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Pharmaceuticals
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CNS-Drugs and Therapy
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CNS-Drugs and Therapy

A special issue of Pharmaceuticals (ISSN 1424-8247).

Deadline for manuscript submissions: closed (30 June 2013) | Viewed by 47492

Special Issue Editor

Prof. Dr. Michael Kassiou

E-Mail Website
Guest Editor
School of Chemistry, Brain and Mind Research Institute, The University of Sydney, Sydney, NSW 2006, Australia
Interests: CNS active molecules; neuroprotective agents; medicinal chemistry and drug discovery; structure-activity relationships of CNS bioactive molecules; rationale CNS drug design and evaluation; heterocyclic chemistry

Special Issue Information

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Published Papers (4 papers)

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Research

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887 KiB  
Article
A Potent (R)-alpha-bis-lipoyl Derivative Containing 8-Hydroxyquinoline Scaffold: Synthesis and Biological Evaluation of Its Neuroprotective Capabilities in SH-SY5Y Human Neuroblastoma Cells
by Ivana Cacciatore, Erika Fornasari, Leonardo Baldassarre, Catia Cornacchia, Stefania Fulle, Ester Sara Di Filippo, Tiziana Pietrangelo and Francesco Pinnen
Pharmaceuticals 2013, 6(1), 54-69; https://doi.org/10.3390/ph6010054 - 7 Jan 2013
Cited by 24 | Viewed by 9497
Abstract
A novel bis-lipoyl derivative containing 8-hydroxyquinoline scaffold (LA-HQ-LA, 5) was synthesized as a new multifunctional drug candidate with antioxidant, chelant, and neuroprotective properties for the treatment of neurodegenerative diseases. We have investigated the potential effectiveness of LA-HQ-LA against the cytotoxicity induced by [...] Read more.
A novel bis-lipoyl derivative containing 8-hydroxyquinoline scaffold (LA-HQ-LA, 5) was synthesized as a new multifunctional drug candidate with antioxidant, chelant, and neuroprotective properties for the treatment of neurodegenerative diseases. We have investigated the potential effectiveness of LA-HQ-LA against the cytotoxicity induced by 6-OHDA and H2O2 on human neuroblastoma SH-SY5Y cell line. Our outcomes showed that LA-HQ-LA resulted in significant neuroprotective and antioxidant effects against H2O2- and 6-OHDA-induced neurotoxicity in human neuroblastoma SH-SY5Y cells, as assessed by MTT assay. In particular, it showed potent neuroprotective effects against 6-OHDA in RA/PMA differentiated cells at all the tested concentrations. Full article
(This article belongs to the Special Issue CNS-Drugs and Therapy)
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Review

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389 KiB  
Review
From Single Target to Multitarget/Network Therapeutics in Alzheimer’s Therapy
by Hailin Zheng, Mati Fridkin and Moussa Youdim
Pharmaceuticals 2014, 7(2), 113-135; https://doi.org/10.3390/ph7020113 - 23 Jan 2014
Cited by 100 | Viewed by 13479
Abstract
Brain network dysfunction in Alzheimer’s disease (AD) involves many proteins (enzymes), processes and pathways, which overlap and influence one another in AD pathogenesis. This complexity challenges the dominant paradigm in drug discovery or a single-target drug for a single mechanism. Although this paradigm [...] Read more.
Brain network dysfunction in Alzheimer’s disease (AD) involves many proteins (enzymes), processes and pathways, which overlap and influence one another in AD pathogenesis. This complexity challenges the dominant paradigm in drug discovery or a single-target drug for a single mechanism. Although this paradigm has achieved considerable success in some particular diseases, it has failed to provide effective approaches to AD therapy. Network medicines may offer alternative hope for effective treatment of AD and other complex diseases. In contrast to the single-target drug approach, network medicines employ a holistic approach to restore network dysfunction by simultaneously targeting key components in disease networks. In this paper, we explore several drugs either in the clinic or under development for AD therapy in term of their design strategies, diverse mechanisms of action and disease-modifying potential. These drugs act as multi-target ligands and may serve as leads for further development as network medicines. Full article
(This article belongs to the Special Issue CNS-Drugs and Therapy)
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144 KiB  
Review
Glibenclamide for the Treatment of Acute CNS Injury
by David B. Kurland, Cigdem Tosun, Adam Pampori, Jason K. Karimy, Nicholas M. Caffes, Volodymyr Gerzanich and J. Marc Simard
Pharmaceuticals 2013, 6(10), 1287-1303; https://doi.org/10.3390/ph6101287 - 11 Oct 2013
Cited by 66 | Viewed by 9108
Abstract
First introduced into clinical practice in 1969, glibenclamide (US adopted name, glyburide) is known best for its use in the treatment of diabetes mellitus type 2, where it is used to promote the release of insulin by blocking pancreatic KATP [sulfonylurea receptor [...] Read more.
First introduced into clinical practice in 1969, glibenclamide (US adopted name, glyburide) is known best for its use in the treatment of diabetes mellitus type 2, where it is used to promote the release of insulin by blocking pancreatic KATP [sulfonylurea receptor 1 (Sur1)-Kir6.2] channels. During the last decade, glibenclamide has received renewed attention due to its pleiotropic protective effects in acute CNS injury. Acting via inhibition of the recently characterized Sur1-Trpm4 channel (formerly, the Sur1-regulated NCCa-ATP channel) and, in some cases, via brain KATP channels, glibenclamide has been shown to be beneficial in several clinically relevant rodent models of ischemic and hemorrhagic stroke, traumatic brain injury, spinal cord injury, neonatal encephalopathy of prematurity, and metastatic brain tumor. Glibenclamide acts on microvessels to reduce edema formation and secondary hemorrhage, it inhibits necrotic cell death, it exerts potent anti-inflammatory effects and it promotes neurogenesis—all via inhibition of Sur1. Two clinical trials, one in TBI and one in stroke, currently are underway. These recent findings, which implicate Sur1 in a number of acute pathological conditions involving the CNS, present new opportunities to use glibenclamide, a well-known, safe pharmaceutical agent, for medical conditions that heretofore had few or no treatment options. Full article
(This article belongs to the Special Issue CNS-Drugs and Therapy)
328 KiB  
Review
The Use of Central Nervous System Active Drugs During Pregnancy
by Bengt Källén, Natalia Borg and Margareta Reis
Pharmaceuticals 2013, 6(10), 1221-1286; https://doi.org/10.3390/ph6101221 - 10 Oct 2013
Cited by 129 | Viewed by 13701
Abstract
CNS-active drugs are used relatively often during pregnancy. Use during early pregnancy may increase the risk of a congenital malformation; use during the later part of pregnancy may be associated with preterm birth, intrauterine growth disturbances and neonatal morbidity. There is also a [...] Read more.
CNS-active drugs are used relatively often during pregnancy. Use during early pregnancy may increase the risk of a congenital malformation; use during the later part of pregnancy may be associated with preterm birth, intrauterine growth disturbances and neonatal morbidity. There is also a possibility that drug exposure can affect brain development with long-term neuropsychological harm as a result. This paper summarizes the literature on such drugs used during pregnancy: opioids, anticonvulsants, drugs used for Parkinson’s disease, neuroleptics, sedatives and hypnotics, antidepressants, psychostimulants, and some other CNS-active drugs. In addition to an overview of the literature, data from the Swedish Medical Birth Register (1996–2011) are presented. The exposure data are either based on midwife interviews towards the end of the first trimester or on linkage with a prescribed drug register. An association between malformations and maternal use of anticonvulsants and notably valproic acid is well known from the literature and also demonstrated in the present study. Some other associations between drug exposure and outcome were found. Full article
(This article belongs to the Special Issue CNS-Drugs and Therapy)
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