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Review

Galantamine as a Potential Treatment for Peripheral Nerve Injuries: Emphasis on Non-Systemic Delivery

by
Mariya Ivanova
1,*,
Liliya Panayotova-Ovcharova
2,
Detelina Nedyalkova-Petkova
2,
Petar Petkov
3,
Georgi Boshev
4 and
Evgeniya Vladeva
2
1
Faculty of Pharmacy, Medical University of Varna, 9000 Varna, Bulgaria
2
Department of Physiotherapy, Rehabilitation and Thalassotherapy, Medical University of Varna, 9000 Varna, Bulgaria
3
Department of Orthopaedics and Traumatology, Medical University of Varna, 9000 Varna, Bulgaria
4
Department of Neurosurgery and ENT, Medical University of Varna, 9000 Varna, Bulgaria
*
Author to whom correspondence should be addressed.
Future Pharmacol. 2025, 5(4), 63; https://doi.org/10.3390/futurepharmacol5040063 (registering DOI)
Submission received: 14 August 2025 / Revised: 10 October 2025 / Accepted: 29 October 2025 / Published: 31 October 2025
Versions Notes

Abstract

Peripheral nerve injuries can lead to significant functional impairments, and treatment options remain limited. Galantamine, widely used for cognitive disorders, has shown potential effects on the peripheral nervous system, making it a candidate for new therapeutic approaches. The narrative review explores the use of galantamine for peripheral nerve injuries, with a focus on transdermal and iontophoretic delivery methods. Searches in scientific databases revealed no peer-reviewed publications addressing this specific application. As a result, the review expanded to include printed and offline sources and a broader timeframe to capture earlier reports. Available evidence from Bulgaria suggests that galantamine ampules have been applied via iontophoresis for peripheral neuropathy. However, this approach is not documented in established scientific databases, and information on its safety and effectiveness is limited. Overall, research on transdermal galantamine for peripheral nerve injuries is still scarce. More studies are needed to better understand its potential benefits and to optimize safe delivery methods.

1. Introduction

Acetylcholinesterase (AChE) inhibitors modulate the hydrolysis of acetylcholine and increase the level and duration of the neurotransmitter’s action [1]. They play a key role in determining cholinergic tone and in exerting their effects on the cholinergic blockade of inflammatory processes. According to the mode of action, AChE inhibitors can be divided into two groups: irreversible and reversible. Reversible inhibitors can be competitive or non-competitive and have primarily therapeutic applications, while toxic effects are associated with irreversible modulators of AChE activity [2]. Reversible AChE inhibitors play an important role in the pharmacological manipulation of enzyme activity [3].
Galantamine is a competitive and reversible inhibitor of acetylcholinesterase that works to increase acetylcholine levels [4]. In addition, the drug is an allosteric ligand of nicotinic cholinergic receptors, causing their modulation. It interacts with the nicotinic receptor at binding sites separate from those for ACh and nicotinic agonists, and acts specifically to increase the activity (sensitization) of nicotinic receptors in the presence of ACh. Galantamine acts both centrally and peripherally to inhibit both muscle and brain acetylcholinesterase, thereby increasing cholinergic tone [5].
Galantamine, belonging to the group of organic compounds known as galanthamine-type amaryllidaceae alkaloids, is isolated from the plant Galanthus woronowii [3]. In 1951, M. D. Mashkovsky and R. P. Kruglikova-Lvova conducted the first pharmacological studies of galantamine. Galantamine was found to be a natural, highly effective anticholinesterase agent. In 1956, galantamine was also extracted from the common snowdrop—Galanthus nivalis L. (D. Paskov, L. Ivanova, Bulgaria) [2]. Galantamine enhances the intrinsic activity of acetylcholine at nicotinic receptors, probably by binding to an allosteric portion of the receptor. As a result, increased activity of the cholinergic system leads to improved cognitive function in patients with Alzheimer’s-type dementia [6,7].
In the late 1950s, numerous preclinical studies on the pharmacological properties of galantamine revealed that galantamine acts as an antagonist of non-depolarizing neuromuscular blockers. In vivo and in vitro experiments are being conducted in rats to determine the effects of galantamine on the brain [8].
Galantamine was first approved in Iceland, Ireland, Sweden, and the UK for the treatment of Alzheimer’s disease in 2000. In 2003, it was approved for use in the US and it is recommended for the symptomatic treatment of mild to moderately severe Alzheimer’s-type dementia. This indication and the possible adverse drug reactions are well known and have been proven by the results of various clinical trials (controlled and open, as well as longitudinal studies to monitor the progression of the disease in a specific group of patients).
Galantamine exists as a capsule. The extended-release form is available in different strengths: 8 mg, 16 mg, and 24 mg. Tablets and solutions are the immediate types of drug-delivering systems. The solution contains 4 mg of galantamine per mL, and the tablet form is available in doses of 4 mg, 8 mg, or 12 mg [4].
Acetylcholinesterase inhibitors (AChEIs) are used off-label, in both adults and pediatric patients, to aid in further neurorecovery after traumatic brain injury [9]. Galantamine has been found to mitigate acute toxicity in non-human primates, indicating its potential neuroprotective effects.
Other conditions aside from the approved ones that can be treated with this medication are vascular dementia [10]; dementia associated with Parkinson’s disease [10]; and frontotemporal dementia [11]. Galantamine alone or along with memantine is an effective treatment for cognitive impairment resulting from traumatic brain injury [12] and for positive, cognitive, and negative symptoms of schizophrenia [13]; it also alleviates some of the symptoms in children with autism [14]. Galantamine treatment is beneficial in chronic post-stroke aphasia and it is an effective antidote against organophosphorus poisoning [15].
Galantamine has been reported to inhibit oxidative stress and inflammation, which are common in various chronic conditions. This opens up potential uses in treating inflammatory disease [16].
Galantamine has been shown to potentiate neurotransmitter release by blocking small conductance Ca2+-activated K+ channels, which could have implications for various neurological conditions [17]. The potential of galantamine to affect various conditions other than Alzheimer’s dementia is being studied [5].

2. Materials and Methods

This narrative review was conducted through a structured search of multiple scientific databases, including PubMed, Google Scholar, EBSCO, MDPI, Cochrane Library, SpringerLink, and ScienceDirect. The primary focus was on literature related to galantamine, with emphasis on non-systemic administration routes, its potential role in peripheral nerve damage, and applications involving iontophoresis. Search terms included combinations of the following keywords: “galantamine,” “Nivalin,” “non-systemic administration,” “peripheral nerve damage,” “iontophoresis,” and “acetylcholinesterase inhibitor.” Boolean operators (AND, OR) were used to refine the search.
The inclusion criteria were as follows:
  • Publications from 2005 to 2025.
  • Articles written in English or Bulgarian.
  • Studies containing clinical or preclinical data on galantamine, including those using its trade name, Nivalin.
  • Relevant research on galantamine’s mechanism of action, delivery methods, and therapeutic applications for nerve damage.
Exclusion criteria were as follows:
  • Studies focused solely on other acetylcholinesterase inhibitors.
  • Publications outside the defined timeframe or in languages other than English/Bulgarian.
  • Irrelevant topics not directly connected to galantamine or its peripheral application.
  • Additional Data Sources
This review also includes an analysis of national clinical guidelines approved for funding by the National Health Insurance Fund (NHIF) in Bulgaria related to the treatment of peripheral nerve damage. Furthermore, publicly accessible data from the NHIF were reviewed to assess the reimbursement and use of galantamine in outpatient care during the period 1 January 2025 to 31 March 2025.
  • Limitations
Due to the limited availability of recent and specific data, particularly concerning non-systemic use and peripheral indications, historical and archival sources—including paper-based materials dating back to 1959—were consulted to support the review. These sources were critically assessed for relevance and credibility.

3. Results

3.1. Clinical Applications of Galantamine

A study of the effect of galantamine after experimental sciatic nerve injury (SCI) in rats demonstrated that pharmacological intervention with galantamine demonstrated a protective effect on degeneration after peripheral nerve injury, but studies in the field are scarce [2].
In Bulgaria, two tablet forms are available: 5 mg (60 tablets) and 10 mg (20 tablets), and ampoule forms: 2.5 mg/1 mL, 5 mg/1 mL, 10 mg/1 mL. As of March 2025, according to NHIF data, only 9 patients in Bulgaria use galamantine for the treatment of Alzheimer’s dementia. The tablet and ampoule forms are used for the treatment of polyradiculoneuritis, radiculoneuritis, neuritis, polyneuritis, polyneuropathies [17]. This medication is used in conditions associated with damage to the anterior horns of the spinal cord (after poliomyelitis, myelitis, spinal muscular atrophy); cerebral palsy (conditions after stroke, infantile cerebral palsy); neuromuscular synapse disorders (myasthenia gravis, muscular dystrophy) [18]; anesthesiology and surgery—to eliminate the effect of non-depolarizing neuromuscular blockers and to treat postoperative paresis of the small intestine and bladder; iontophoretic physiotherapy is used to address neurological damage to the peripheral nervous system and nocturnal enuresis [19].
According to the guidelines in the country, treatment for all acute neuritis and neuropathies begins immediately, within the first 10–15 days, with galamantine as the second choice, administered on a schedule. Plexitis is treated with galamantine i.m. according to a scheme, vitamins from group B (B1-30 mg, B6-0.1 g, B12-1000 μg daily intramuscularly) and physiotherapy. In case of sensory and motor symptoms, cholinergic drugs can be used (galamantine according to an ascending–descending scheme for 30–90 days) [20]. According to official data released by the National Health Insurance Fund for the period 1 January–31 March 2025, galantamine tablets (5 mg and 10 mg) were most frequently prescribed for the treatment of diabetic polyneuropathy G 63.2 81.16%; N = 1221 of patients; G 54.4 Lumbosacral root disorders, not elsewhere classified 7.75%; N = 117 and G 54.1 Lumbosacral plexus disorders 4.77%; N = 72 [19].

3.2. Transdermal Delivery Methods to Minimize Adverse Effects

Oral administration of medicinal products containing galantamines leads to gastrointestinal issues. The most frequently reported side effects include nausea (20%), vomiting (10%), and diarrhea (5–7%). These effects are likely due to galantamine’s action on the gastrointestinal tract, causing disturbances in motility and smooth muscle contractions. Studies have shown that galantamine affects gastric myoelectric activity, which may explain gastrointestinal side effects in humans. Another common side effect is dyspepsia. galamantine has been shown to negatively affect gastric myoelectric activity, which could explain the dyspepsia observed in some patients. Mild side effects such as headache and appetite suppression have also been reported [21].
While galantamine can improve cognitive functions in Alzheimer’s patients, it can also cause side effects such as anxiety, agitation, and hallucinations. In some cases, it has been associated with nightmares and anxiety, particularly with rapid dose titration 8. Motor Symptoms: in patients with Parkinson’s disease, galantamine has been associated with worsening of motor symptoms and gastrointestinal side effects, leading to a high dropout rate in clinical trials [22].
Other side effects have been observed in a subset of patients, along with nausea and dysuria. Some patients have reported improvements in sleep, while others experienced sleep-related issues such as nightmares.
Comparison between the oral and intranasal routes of galantamine (GLH) confirms that adverse effects associated with the oral route are due to interaction in the gastrointestinal tract and not to systemic exposure of the drug [23]. To avoid gastrointestinal side effects associated with oral administration, intranasal delivery of galantamine using chitosan-based nanoparticles has been explored. This method could provide a more patient-friendly and efficient delivery system [24].
Another method under development is the buccal administration of galantamine [24].
Transdermal and intranasal delivery of galantamine represent promising alternatives to oral administration, with demonstrated benefits in avoiding systemic side effects and potentially enhancing patient compliance [25,26].
For the treatment of Alzheimer’s disease (AD), the FDA has approved transdermal patches containing acetylcholinesterase inhibitors, such as donepezil and rivastigmine. Donepezil patches are replaced weekly [27], while rivastigmine patches are replaced daily. These patches have been shown to improve cognitive symptoms within a short period and minimize drug interactions [28].
Research, both in vitro and in vivo, has been conducted to identify the most suitable form for transdermal administration, including studies on gel formulations and the characteristics of transdermal systems. It was initially found that the free form of galantamine is more readily absorbed during transdermal administration, posing a challenge, since galantamine hydrobromide is primarily used [29].
Plasma concentrations of galantamine (GLT) after intravenous administration at a dose of 5 mg/kg decrease rapidly, becoming minimal after 4 h. Oral administration of GLT is quickly absorbed from the gastrointestinal tract, reaching a maximum concentration (Cmax) of 254.01 ± 16.46 ng/mL at a time to peak concentration (Tmax) of 0.50 ± 0.00 h (mean ± SD, n = 3). However, these plasma concentrations also decline rapidly and become undetectable after 6 h. In contrast, after transdermal administration, plasma concentrations of GLT rise quickly, reaching a Cmax of approximately 21.8–112.1 ng/mL, with a Tmax of approximately 2.0–5.6 h. During the wear time of the patch (up to 12 h), the plasma levels of different GLT patch models remained stable, ranging from 14 to 112 ng/mL, before decreasing until patch removal at 24 h [30].
In a study that monitored the effect of galantamine (GLH) administered transdermally on rheumatoid arthritis (RA), RA was induced in Sprague-Dawley rats through intradermal injection. The rats received oral growth hormone (GH) at 1.25 mg/kg/day and a transdermal GH patch at 2.5 mg/kg every 2 days for 14 days, during which hindpaw swelling and body weight (BW) were assessed [31]. The study evaluated the effects on C-reactive protein (CRP), inflammatory cytokines (TNF-α, IL-10, and IL-1β), and Janus kinase (JAK-2). Both oral and transdermal GLH treatments significantly reduced hindpaw swelling in the arthritis model and provided protective effects against RA. However, the oral GLH group experienced a significant decrease in body weight compared to the transdermal patch group, which showed a more significant reduction in IL-1β levels than the oral group. There was no significant difference in TNF-α and IL-10 levels between the two treatment groups [31].
According to the studies, the optimal gel formulation for the patch reservoir was found to contain 0.89% w/w carbopol, 1.16% w/w triethanolamine, and 4.19% w/w GH. Optimization analysis indicated that this formulation had a predicted cumulative drug release rate of 17.80 mg·cm2 at 8 h, with a predicted permeation flux of 2.27 mg·cm2/h. These predicted values closely matched the actual cumulative drug release rate (16.93 ± 0.08 mg·cm2) and the actual permeation flux (2.32 ± 0.02 mg·cm2/h) observed in experiments [32].
Scientific studies showed that the optimized patch contained 8% GLT and 3% oleic acid, resulting in high absolute bioavailability (80%) and stable plasma GLT levels over an extended period (24 h) with these patches.
Preclinical studies have successfully formulated galantamine gel and patch systems, achieving sustained release and adequate bioavailability [30].
A summary of transdermal innovative delivery systems for galantamine is presented in Table 1.

3.3. The Potential Benefits of Using Galantamine Topically

The numerous side effects of this medication necessitate the search for alternative drug delivery systems and alternative routes of administration, in order to avoid the digestive system and passage through hepatic metabolism. Transdermal administration reduces gastrointestinal side effects [21].
The advantages of transdermal application are as follows: Topical administration is non-invasive and can be self-administered, which may improve patient compliance and convenience. Topical application can potentially reduce systemic side effects compared to oral administration. This is particularly relevant for drugs like galantamine, which can cause gastrointestinal side effects when taken orally [41].
Localized effect: topical application allows for localized drug delivery, which could be beneficial for treating conditions with localized symptoms or for targeting specific areas, such as in the case of neurodegenerative diseases affecting specific brain regions [32].
Avoidance of first-pass metabolism: topical administration bypasses the liver’s first-pass metabolism, potentially increasing the bioavailability of the drug and allowing for lower doses to achieve therapeutic effects.
Potential neuroprotective effects: galantamine has demonstrated neuroprotective effects in various studies, including protection against amyloid-β-induced toxicity and peripheral nerve degeneration [10,42]. These properties could be beneficial if the drug can be effectively delivered to the target tissues through the skin.
Studies indicate that by modifying carriers for dermal administration, a systemic effect can be obtained [43]. Transdermal drug delivery systems are expected to improve patient compliance.
Challenges and considerations include skin penetration. The primary challenge for topical administration is the drug’s ability to penetrate the skin barrier, particularly the stratum corneum. Enhancers and advanced delivery systems like nanoparticles or vesicles may be required to improve penetration. Formulation: the formulation of the topical preparation is crucial. Factors such as the drug’s physicochemical properties, the choice of excipients, and the delivery system can significantly affect the drug’s ability to permeate the skin and reach the target tissues.

3.4. Use of Galantamine by Transdermal Deposition in Physiotherapy

Iontophoresis enhances transdermal drug penetration by applying a low-intensity electric current, facilitating the movement of ionized drug molecules through the stratum corneum. This mechanism is particularly advantageous for hydrophilic, ionizable compounds such as galantamine, which exhibit limited passive diffusion across intact skin barriers. Iontophoresis is suitable for drugs that are ionically active (charged particles, as is the case with galantamine [20,27,44,45].
In conjunction with other therapeutic regimens, galantamine with iontophoresis is indicated for improving neuromuscular conduction in peripheral nervous system damage, aiding in the recovery of traumatic plexitis, and has an unblocking effect on traumatic damage to the lumbosacral plexus and its individual nerves (n. sciaticus; n. tibialis; n. fibularis) [46]. Table 2 presents the method used for the introduction of galantamine, by iontophoresis [21].
Iontophoresis with galantamine follows the following administration algorithm: 1. Preparation of the solution: An aqueous solution of galantamine hydrobromide is used. The concentration is usually 0.25–1% (depending on the prescription) according to Yasnogorodsky V.G. 1990 [47]. The pH of the solution is maintained at a slightly acidic to neutral value (pH ~5–6). 2. Selection of electrodes: Galamantine is positively charged (cation), so it is applied under the anode (positive electrode). The active electrode is placed on the skin in the area where local action is desired. The passive electrode is placed elsewhere to close the electrical circuit. 3. Device settings: Current: 0.5–5 mA, depending on the patient’s sensitivity. Duration: 10–20 min. Type of current: galvanic (constant). 4. Frequency of procedures: usually applied daily or every other day, with one course of 10 to 15 procedures [48].
The application may vary depending on the condition. In peripheral neuritis, due to infection, rheumatism, and trauma, treatment is allowed after 20 days. Current intensity: 6–16 mA; duration: 20 sessions of 6–16 min. In polyneuritis caused by infections; exogenous intoxications, endogenous intoxications; vegetative polyneuritis; and colds, longitudinal electrophoresis is performed to prevent connective tissue growths and transverse electrophoresis of the spine. Thirty to thirty-five procedures are performed with a duration of 10–30 min [46].

3.5. Advantages of Using Iontophoresis for Galantamine

The advantages are painless and non-invasive application. Iontophoresis provides a non-invasive alternative to oral or injectable routes, which can be particularly beneficial for patients with swallowing difficulties or those requiring long-term medication [49].
Gastrointestinal irritation is avoided. Local accumulation of the medication is allowed. The medication is suitable for patients with liver/stomach problems. The technique allows for controlled and sustained drug delivery, which can improve therapeutic outcomes and reduce the side effects associated with fluctuating drug levels [50,51]. Iontophoresis significantly enhances the permeation of galantamine through the skin or mucosa, overcoming barriers that limit the effectiveness of conventional delivery methods [51].
Contraindications for this therapy include skin lesions at the site of application, tumor processes, pregnancy (with caution), a pacemaker, and metal implants in the area.

4. Discussion

The findings from the reviewed literature and policy documents suggest that galantamine has potential clinical utility beyond its established role in cognitive disorders. While its systemic use in Alzheimer’s disease is well-documented and approved in multiple countries, its historical and current use in Eastern Europe—particularly in Bulgaria—includes indications such as peripheral nerve damage. This broader therapeutic application appears to be underexplored in modern Western literature, yet it is supported by decades of clinical experience in Bulgaria [19].
When administered orally, galantamine causes adverse drug reactions that compromise compliance and adherence to therapy. As a result, alternative routes of administration, such as non-systemic and dermal administration, are of increasing interest. Iontophoresis, in particular, has shown promise as a technique for enhancing transdermal absorption of galantamine without the need for invasive procedures or oral dosing. However, robust clinical evidence in this area remains scarce and largely preclinical or anecdotal.
The Bulgarian clinical context offers a unique case study. Galantamine is still used for peripheral nerve recovery, and its inclusion in NHIF-funded treatment protocols demonstrates its continued relevance in national healthcare. Notably, data from the first quarter of 2025 show active reimbursement for outpatient treatment with galantamine, which may reflect both physician confidence in its efficacy and its availability within the public health system [19]. However, the lack of recent high-quality randomized controlled trials (RCTs) or modern pharmacokinetic studies in the context of non-systemic application highlights a significant evidence gap.
Another limitation is the reliance on historical and paper-based data, some dating back as far as 1959. While these sources provide valuable insight into long-term clinical practices, they do not always meet current standards for evidence-based medicine. The absence of harmonized international guidelines for the use of galantamine in peripheral nerve disorders further underscores the need for updated research, including modern delivery methods such as iontophoresis and comparative studies with other neuroregenerative agents.
Overall, while preliminary evidence and historical usage support the feasibility of galantamine in treating peripheral nerve damage—especially via non-systemic delivery—the current literature is insufficient to support broad clinical recommendations. Further studies are needed to evaluate its safety, efficacy, and pharmacodynamics when applied locally, as well as its cost-effectiveness in national health systems.
Despite the continued use of the methodology in the rehabilitation of large groups of patients with peripheral nervous system damage, there is a need for clinical trials on modern medical approaches. There is a lack of clinical data specifically evaluating the efficacy and safety of topical galantamine. More research is needed to establish optimal formulations, dosing regimens, and therapeutic outcomes.

5. Conclusions

Galantamine has been primarily utilized in the management of Alzheimer’s disease due to its role as a reversible acetylcholinesterase inhibitor. However, alternative delivery routes, such as transdermal and intranasal administration, offer promising non-oral approaches that may reduce systemic side effects and enhance patient adherence. Moreover, these methods hold the potential to broaden the therapeutic applications of galantamine beyond neurodegenerative disorders.
Despite some preliminary evidence suggesting its potential benefits in the treatment of peripheral nervous system injuries, there is a notable lack of robust, contemporary studies specifically investigating the efficacy and safety of topical galantamine for this patient population. While the theoretical advantages of non-invasive administration, reduced gastrointestinal irritation, and localized drug delivery are compelling, significant challenges persist—most notably, achieving adequate skin permeability and maintaining therapeutic concentrations at the target tissue.
To fully harness the potential of topical galantamine, further rigorous research is required, including the development of advanced transdermal delivery systems capable of optimizing bioavailability and clinical outcomes in neurological and peripheral nerve disorders.

Author Contributions

Conceptualization, M.I., L.P.-O. and D.N.-P.; methodology, M.I.; software, M.I. and P.P.; validation, L.P.-O., D.N.-P. and G.B.; formal analysis, M.I. and L.P.-O.; investigation, M.I.; resources, M.I.; data curation, P.P.; writing—original draft preparation, M.I., D.N.-P., P.P. and L.P.-O.; writing—review and editing, M.I., D.N.-P. and E.V.; visualization, P.P. and G.B.; supervision, E.V.; project administration, L.P.-O.; funding acquisition, L.P.-O. All authors have read and agreed to the published version of the manuscript.

Funding

This study is financed by the European Union-NextGeneration EU, through the National Recovery and Resilience Plan of the Republic of Bulgaria, project No. BG-RRP-2.004-0009-C02.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Conflicts of Interest

The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Abbreviations

The following abbreviations are used in this manuscript:
AChEAcetylcholinesterase
AChEIsAcetylcholinesterase inhibitors
ADAlzheimer’s disease
RARheumatoid arthritis
NHIFNational Health Insurance Fund
SCISciatic nerve injury

References

  1. Olazarán, J.; García, G. Galantamine: A novel cholinergic agent for Alzheimer’s disease. Neurologia 2002, 17, 429–436. [Google Scholar]
  2. Kalola, U.K.; Patel, P.; Nguyen, H. Galantamine. In StatPearls; StatPearls Publishing: Treasure Island, FL, USA, 2025. Available online: http://www.ncbi.nlm.nih.gov/books/NBK574546/ (accessed on 14 August 2025).
  3. Libro, R.; Giacoppo, S.; Rajan, T.S.; Bramanti, P.; Mazzon, E. Natural Phytochemicals in the Treatment and Prevention of Dementia: An Overview. Molecules 2016, 21, 518. [Google Scholar] [CrossRef]
  4. FDA-Approved Drugs to Treat Dementia. J. Psychosoc. Nurs. Ment. Health Services 2025, 63, 7–8. [CrossRef]
  5. Mucke, H.A. The case of galantamine: Repurposing and late blooming of a cholinergic drug. Future Sci. OA 2015, 1, FSO73. [Google Scholar] [CrossRef] [PubMed]
  6. Cummings, J.L. Treatment of Alzheimer’s disease: Current and future therapeutic approaches. Rev. Neurol. Dis. 2004, 1, 60–69. [Google Scholar]
  7. Bokov, D.O. Standardization of Snowdrop (Galanthus L.) Herbal Pharmaceutical Substances by UV-Spectrophotometry. Asian J. Pharm. Clin. Res. 2018, 11, 207–211. [Google Scholar] [CrossRef]
  8. Handzhieva-Darlenska, T.; Belcheva, V.; Grigorov, E. Galantamine–An Effective Choice for Symptomatic Treatment of Mild to Moderately Severe Alzheimer’s Dementia-Medical Review. Available online: http://hdl.handle.net/10861/1346 (accessed on 20 June 2025).
  9. Corey-Bloom, J. Galantamine: A review of its use in Alzheimer’s disease and vascular dementia. Int. J. Clin. Pract. 2003, 57, 219–223. [Google Scholar] [CrossRef]
  10. Aarsland, D.; Hutchinson, M.; Larsen, J.P. Cognitive, psychiatric and motor response to galantamine in Parkinson’s disease with dementia. Int. J. Geriatr. Psychiatry 2003, 18, 937–941. [Google Scholar] [CrossRef]
  11. Kertesz, A.; Morlog, D.; Light, M.; Blair, M.; Davidson, W.; Jesso, S.; Brashear, R. Galantamine in frontotemporal dementia and primary progressive aphasia. Dement. Geriatr. Cogn. Disord. 2008, 25, 178–185. [Google Scholar] [CrossRef]
  12. de la Tremblaye, P.B.; Wellcome, J.L.; de Witt, B.W.; Cheng, J.P.; Skidmore, E.R.; Bondi, C.O.; Kline, A.E. Rehabilitative success after brain trauma by augmenting a sub-therapeutic dose of environmental enrichment with galantamine. Neurorehabil. Neural Repair 2017, 31, 977–985. [Google Scholar] [CrossRef]
  13. Koola, M.M. Potential Role of Antipsychotic-Galantamine-Memantine Combination in the Treatment of Positive, Cognitive, and Negative Symptoms of Schizophrenia. Mol. Neuropsychiatry 2018, 4, 134–148. [Google Scholar] [CrossRef] [PubMed]
  14. Ghaleiha, A.; Ghyasvand, M.; Mohammadi, M.R.; Farokhnia, M.; Yadegari, N.; Tabrizi, M.; Hajiaghaee, R.; Yekehtaz, H.; Akhondzadeh, S. Galantamine efficacy and tolerability as an augmentative therapy in autistic children: A randomized, double-blind, placebo-controlled trial. J. Psychopharmacol. 2014, 28, 677–685. [Google Scholar] [CrossRef]
  15. Pereira, E.F.R.; Aracava, Y.; Alkondon, M.; Akkerman, M.; Merchenthaler, I.; Albuquerque, E.X. Molecular and cellular actions of galantamine: Clinical implications for treatment of organophosphorus poisoning. J. Mol. Neurosci. 2010, 40, 196–203. [Google Scholar] [CrossRef]
  16. Chang, E.H.; Chavan, S.S.; Pavlov, V.A. Cholinergic Control of Inflammation, Metabolic Dysfunction, and Cognitive Impairment in Obesity-Associated Disorders: Mechanisms and Novel Therapeutic Opportunities. Front. Neurosci. 2019, 13, 263. [Google Scholar] [CrossRef]
  17. National Council on Prices and Reimbursement of Medicinal Products. Register of Marginal Prices. Available online: https://portal.ncpr.bg/registers/pages/register/list-medicament.xhtml (accessed on 15 March 2025).
  18. Lombardo, G.; Arena, G. The use of galantamine bromhydrate (nivaline) in the paralytic sequelae of poliomyelitis, neuraxitis and in muscular dystrophy. Minerva Pediatr. 1962, 14, 724–728. [Google Scholar]
  19. National Health Insurance Fund. List of Medicinal Products that the NHIF Pays for Under Regulation No. 10/2009. Available online: https://www.nhif.bg/bg/medicine_food/medical-list/2024 (accessed on 1 April 2025).
  20. Pharmacotherapeutic Guide for the Treatment of Neurological Diseases. Available online: https://www.ncpr.bg/images/farmako-terapevtichni/2019/01.04.2019/ftr_za_lechenie_na_nevrologichnite_zaboliavaniia.pdf (accessed on 1 April 2025).
  21. Ruangritchankul, S.; Chantharit, P.; Srisuma, S.; Gray, L.C. Adverse Drug Reactions of Acetylcholinesterase Inhibitors in Older People Living with Dementia: A Comprehensive Literature Review. Ther. Clin. Risk Manag. 2021, 17, 927–949. [Google Scholar] [CrossRef]
  22. RAZADYNE (galantamine hydrobromide). Available online: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=021169 (accessed on 10 April 2025).
  23. Kandil, L.S.; Hanafy, A.S.; Abdelhady, S.A. Galantamine transdermal patch shows higher tolerability over oral galantamine in rheumatoid arthritis rat model. Drug Dev. Ind. Pharm. 2020, 46, 996–1004. [Google Scholar] [CrossRef]
  24. Georgieva, D.; Nikolova, D.; Vassileva, E.; Kostova, B. Chitosan-Based Nanoparticles for Targeted Nasal Galantamine Delivery as a Promising Tool in Alzheimer’s Disease Therapy. Pharmaceutics 2023, 15, 829. [Google Scholar] [CrossRef]
  25. Varadharajan, A.; Davis, A.D.; Ghosh, A.; Jagtap, T.; Xavier, A.; Menon, A.J.; Roy, D.; Gandhi, S.; Gregor, T. Guidelines for pharmacotherapy in Alzheimer’s disease-A primer on FDA-approved drugs. J. Neurosci. Rural Pract. 2023, 14, 566–573. [Google Scholar] [CrossRef]
  26. WeMihailova, D.; Yamboliev, I.; Zhivkova, Z.; Tencheva, J.; Jovovich, V. Pharmacokinetics of galanthamine hydrobromide after single subcutaneous and oral dosage in humans. Pharmacology 1989, 39, 50–58. [Google Scholar] [CrossRef]
  27. Kale, M.; Kipping, T.; Banga, A.K. Modulated delivery of donepezil using a combination of skin microporation and iontophoresis. Int. J. Pharm. 2020, 589, 119853. [Google Scholar] [CrossRef]
  28. Sozio, P.; Cerasa, L.S.; Marinelli, L.; Di Stefano, A. Transdermal donepezil on the treatment of Alzheimer’s disease. Neuropsychiatr. Dis. Treat. 2012, 8, 361–368. [Google Scholar] [CrossRef]
  29. Woo, F.Y.; Basri, M.; Masoumi, H.R.F.; Ahmad, M.B.; Ismail, M. Formulation optimization of galantamine hydrobromide loaded gel drug reservoirs in transdermal patch for Alzheimer’s disease. Int. J. Nanomed. 2015, 10, 103879–103886. [Google Scholar] [CrossRef]
  30. Ghosh, B.; Tanweer, S.; Das, S.; Dey, C.; Mondal, A.; Dey, S.; Jaman, S.; Mohanty, D.; Baksi, S.; Mondal, A.; et al. A development and evaluation of nanofiber patch of galantamine for transdermal drug delivery: Box Behnken design optimized. Next Res. 2025, 2, 100413. [Google Scholar] [CrossRef]
  31. Gowayed, M.A.; Refaat, R.; Ahmed, W.M.; El-Abhar, H.S. Effect of galantamine on adjuvant-induced arthritis in rats. Eur. J. Pharmacol. 2015, 764, 547–553. [Google Scholar] [CrossRef]
  32. Park, C.W.; Son, D.D.; Kim, J.Y.; Oh, T.O.; Ha, J.M.; Rhee, Y.S.; Park, E.S. Investigation of formulation factors affecting in vitro and in vivo characteristics of a galantamine transdermal system. Int. J. Pharm. 2012, 436, 32–40. [Google Scholar] [CrossRef]
  33. Fornaguera, C.; Dols-Perez, A.; Calderó, G.; García-Celma, M.J.; Camarasa, J.; Solans, C. PLGA nanoparticles prepared by nano-emulsion templating using low-energy methods as efficient nanocarriers for drug delivery across the blood-brain barrier. J. Control. Release 2015, 211, 134–143. [Google Scholar] [CrossRef]
  34. Hanafy, A.S.; Farid, R.M.; Helmy, M.W.; ElGamal, S.S. Pharmacological, toxicological and neuronal localization assessment of galantamine/chitosan complex nanoparticles in rats: Future potential contribution in Alzheimer’s disease management. Drug Deliv. 2016, 23, 3111–3122. [Google Scholar] [CrossRef]
  35. Kostelnik, A.; Kopel, P.; Cegan, A.; Pohanka, M. Construction of an Acetylcholinesterase Sensor Based on Synthesized Paramagnetic Nanoparticles, a Simple Tool for Neurotoxic Compounds Assay. Sensors 2017, 17, 676. [Google Scholar] [CrossRef]
  36. Ameen, D.; Michniak-Kohn, B. Development and in vitro evaluation of pressure sensitive adhesive patch for the transdermal delivery of galantamine: Effect of penetration enhancers and crystallization inhibition. Eur. J. Pharm. Biopharm. 2019, 139, 262–271. [Google Scholar] [CrossRef]
  37. Mufamadi, M.S.; Kumar, P.; du Toit, L.C.; Choonara, Y.E.; Obulapuram, P.K.; Modi, G. Liposome-embedded, polymeric scaffold for extended delivery of galantamine. J. Drug Deliv. Sci. Technol. 2019, 50, 255–265. [Google Scholar] [CrossRef]
  38. Siafaka, P.I.; Bülbül, E.Ö.; Mutlu, G.; Okur, M.E.; Karantas, I.D.; Okur, N.Ü. Transdermal Drug Delivery Systems and their Potential in Alzheimer’s Disease Management. CNS Neurol. Disord. Drug Targets 2020, 19, 360–373. [Google Scholar] [CrossRef]
  39. Kandil, L.S.; Farid, R.M.; ElGamal, S.S.; Hanafy, A.S. Intranasal galantamine/chitosan complex nanoparticles elicit neuroprotection potentials in rat brains via antioxidant effect. Drug Dev. Ind. Pharm. 2021, 47, 735–740. [Google Scholar] [CrossRef]
  40. Basso, L.; Fagundes, S.C.; Staudt, T.; da Rosa, K.; Langaro, E.; Omidian, H.; Bertol, C.D. Transdermal Therapeutic Systems for the Treatment of Alzheimer’s Disease: A Patent Review. CNS Neurol. Disord. Drug Targets 2024, 23, 1075–1084. [Google Scholar] [CrossRef]
  41. Yen, W.F.; Basri, M.; Ahmad, M.; Ismail, M. Formulation and evaluation of galantamine gel as drug reservoir in transdermal patch delivery system. Sci. World J. 2015, 2015, 495271. [Google Scholar] [CrossRef]
  42. Lopes, J.P.; Tarozzo, G.; Reggiani, A.; Piomelli, D.; Cavalli, A. Galantamine potentiates the neuroprotective effect of memantine against NMDA-induced excitotoxicity. Brain Behav. 2013, 3, 67–74. [Google Scholar] [CrossRef]
  43. Nguyen, T.T.; Giau, V.V.; Vo, T.K. Current advances in transdermal delivery of drugs for Alzheimer’s disease. Indian J. Pharmacol. 2017, 49, 145–154. [Google Scholar] [CrossRef]
  44. Singhal, M.; Merino, V.; Rosini, M.; Cavalli, A.; Kalia, Y.N. Controlled Iontophoretic Delivery in Vitro and in Vivo of ARN14140-A Multitarget Compound for Alzheimer’s Disease. Mol. Pharm. 2019, 16, 3460–3468. [Google Scholar] [CrossRef]
  45. Ulashchik, V.S. Theory and Practice of Medicinal Electrophoresis; V.S. Ulashchyk: Minsk, Belarus, 1976. [Google Scholar]
  46. Gatev, S.; Bankov, S.; Busarov, S. Manual of Physical Therapy; Medicine and Physical Education: Sofia, Bulgaria, 1992. [Google Scholar]
  47. Yasnogorodski, V. Handbook of Physiotherapy; Moscow Medicine: Moscow, Russia, 1990. [Google Scholar]
  48. Nikolova, L. Special Physiotherapy; Medicine and Physical Education: Sofia, Bulgaria, 1978. [Google Scholar]
  49. Gross, I.P.; Lima, A.L.; Sá-Barreto, L.L.; Gelfuso, G.M.; Cunha-Filho, M. Recent advances in cutaneous drug delivery by iontophoresis. Expert Opin. Drug Deliv. 2025, 22, 857–874. [Google Scholar] [CrossRef]
  50. Krueger, E.; Junior, J.L.C.; Scheeren, E.M.; Neves, E.B.; Mulinari, E.; Nohama, P. Iontophoresis: Principles and applications. Fisioter. Mov. 2014, 27, 469–481. [Google Scholar] [CrossRef]
  51. Krnjević, K.; Phillis, J.W. Iontophoretic studies of neurones in the mammalian cerebral cortex. J. Physiol. 1963, 165, 274–304. [Google Scholar] [CrossRef]
Table 1. Innovative drug delivery technologies for galamantine.
Table 1. Innovative drug delivery technologies for galamantine.
YearDrug Delivery systemFormulation ApproachReference
2015Transdermal gel reservoir patchFormulation of gel reservoirs for controlled galantamine releaseWoo FY [29]
2015PLGA nanoparticles (nanoemulsion templating)Nanoemulsion-based PLGA nanoparticles with galantamineFornaguera C [33]
2016Galantamine/chitosan complex nanoparticlesImproved brain targeting and reduced toxicityHanafy AS [24,34]
2017Nanoparticle acetylcholinesterase sensorNanoparticles for neurotoxin detection and diagnostic applicationsKostelnik A [35]
2019Transdermal adhesive patch with penetration enhancersUse of enhancers and crystallization inhibitors for better absorptionAmeen D [36]
2019Liposome-embedded polymeric scaffoldDevelopment of a polymeric scaffold incorporating liposomes for extended and controlled galantamine releaseMufamadi S [37]
2020Transdermal patch–preclinical modelHigher tolerability than oral form in rheumatoid arthritis rat modelKandil LS [23]
2020Review of transdermal drug delivery systemsReview of transdermal DDS potential for neurodegenerative diseasesSiafaka PI [38]
2021Intranasal chitosan nanoparticlesIntranasal delivery with antioxidant and neuroprotective effectsKandil LS [39]
2024Transdermal therapeutic systems (patent review)Overview of patents and innovations for galantamine transdermal deliveryBasso L [40]
Table 2. Stages of galantamine administration by iontophoresis.
Table 2. Stages of galantamine administration by iontophoresis.
ParameterDescription
Pharmaceutical AgentGalantamine hydrobromide–reversible acetylcholinesterase inhibitor
Solution CharacteristicsAqueous solution (0.25–1%); pH maintained between 5.0 and 6.0 to optimize iontophoretic transport
Electrochemical ConsiderationGalantamine, as a cation, is delivered via the anode (positive electrode)
Electrode PlacementActive electrode: target dermal site (e.g., cervical, lumbar, extremities). Passive electrode: contralateral or distal position
Device ParametersCurrent intensity: 0.5–5 mA (patient-dependent tolerance); application time: 10–20 min; current type: constant direct current (galvanic)
Treatment RegimenFrequency: daily or every other day; duration: 10–15 sessions per therapeutic cycle
Clinical AdvantagesMinimally invasive transdermal drug delivery; reduction in systemic gastrointestinal exposure; potential for localized drug accumulation; well suited for patients with hepatic or gastrointestinal contraindications
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Ivanova, M.; Panayotova-Ovcharova, L.; Nedyalkova-Petkova, D.; Petkov, P.; Boshev, G.; Vladeva, E. Galantamine as a Potential Treatment for Peripheral Nerve Injuries: Emphasis on Non-Systemic Delivery. Future Pharmacol. 2025, 5, 63. https://doi.org/10.3390/futurepharmacol5040063

AMA Style

Ivanova M, Panayotova-Ovcharova L, Nedyalkova-Petkova D, Petkov P, Boshev G, Vladeva E. Galantamine as a Potential Treatment for Peripheral Nerve Injuries: Emphasis on Non-Systemic Delivery. Future Pharmacology. 2025; 5(4):63. https://doi.org/10.3390/futurepharmacol5040063

Chicago/Turabian Style

Ivanova, Mariya, Liliya Panayotova-Ovcharova, Detelina Nedyalkova-Petkova, Petar Petkov, Georgi Boshev, and Evgeniya Vladeva. 2025. "Galantamine as a Potential Treatment for Peripheral Nerve Injuries: Emphasis on Non-Systemic Delivery" Future Pharmacology 5, no. 4: 63. https://doi.org/10.3390/futurepharmacol5040063

APA Style

Ivanova, M., Panayotova-Ovcharova, L., Nedyalkova-Petkova, D., Petkov, P., Boshev, G., & Vladeva, E. (2025). Galantamine as a Potential Treatment for Peripheral Nerve Injuries: Emphasis on Non-Systemic Delivery. Future Pharmacology, 5(4), 63. https://doi.org/10.3390/futurepharmacol5040063

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