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Pharmaceutics 2013, 5(2), 318-328; doi:10.3390/pharmaceutics5020318
Communication

Design and Exploratory Neuropharmacological Evaluation of Novel Thyrotropin-Releasing Hormone Analogs and Their Brain-Targeting Bioprecursor Prodrugs

1,2,* , 1
, 1
, 1,†
 and 1
Received: 21 March 2013; in revised form: 7 May 2013 / Accepted: 10 May 2013 / Published: 22 May 2013
(This article belongs to the Special Issue Prodrugs)
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Abstract: Efforts to take advantage of the beneficial activities of thyrotropin-releasing hormone (TRH) in the brain are hampered by its poor metabolic stability and lack of adequate central nervous system bioavailability. We report here novel and metabolically stable analogs that we derived from TRH by replacing its amino-terminal pyroglutamyl (pGlu) residue with pyridinium-containing moieties. Exploratory studies have shown that the resultant compounds were successfully delivered into the mouse brain after systemic administration via their bioprecursor prodrugs, where they manifested neuropharmacological responses characteristic of the endogenous parent peptide. On the other hand, the loss of potency compared to TRH in a model testing antidepressant-like effect with a simultaneous preservation of analeptic activity has been observed, when pGlu was replaced with trigonelloyl residue. This finding may indicate an opportunity for designing TRH analogs with potential selectivity towards cholinergic effects.
Keywords: bioprecursor prodrug; brain-targeting delivery; thyrotropin-releasing hormone; synthetic peptide analog; analeptic effect; antidepressant-like activity bioprecursor prodrug; brain-targeting delivery; thyrotropin-releasing hormone; synthetic peptide analog; analeptic effect; antidepressant-like activity
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Prokai-Tatrai, K.; Nguyen, V.; Szarka, S.; Konya, K.; Prokai, L. Design and Exploratory Neuropharmacological Evaluation of Novel Thyrotropin-Releasing Hormone Analogs and Their Brain-Targeting Bioprecursor Prodrugs. Pharmaceutics 2013, 5, 318-328.

AMA Style

Prokai-Tatrai K, Nguyen V, Szarka S, Konya K, Prokai L. Design and Exploratory Neuropharmacological Evaluation of Novel Thyrotropin-Releasing Hormone Analogs and Their Brain-Targeting Bioprecursor Prodrugs. Pharmaceutics. 2013; 5(2):318-328.

Chicago/Turabian Style

Prokai-Tatrai, Katalin; Nguyen, Vien; Szarka, Szabolcs; Konya, Krisztina; Prokai, Laszlo. 2013. "Design and Exploratory Neuropharmacological Evaluation of Novel Thyrotropin-Releasing Hormone Analogs and Their Brain-Targeting Bioprecursor Prodrugs." Pharmaceutics 5, no. 2: 318-328.



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