Neuropharmacodynamic evaluation of the centrally active thyrotropin-releasing hormone analogue [Leu 2]TRH and its chemical brain-targeting system

The centrally active thyrotropin-releasing hormone (TRH) analogue pGlu–Leu–Pro–NH 2 ([Leu 2]TRH) showed a significant increase in the extracellular acetylcholine concentration during its perfusion to the hippocampus in rats, and this effect was manifested upon the delivery of the analogue in much sm...

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Bibliographic Details
Published in:Brain research 2002-10, Vol.952 (2), p.268-274
Main Authors: Prokai, Laszlo, Zharikova, Alevtina D
Format: Article
Language:English
Subjects:
Acetylcholine
Acetylcholine - metabolism
Animals
Biological and medical sciences
Brain - drug effects
Brain - metabolism
Brain-delivery
Central nervous system
Central neurotransmission. Neuromudulation. Pathways and receptors
Drug Delivery Systems - methods
Drug Evaluation, Preclinical - methods
Fundamental and applied biological sciences. Psychology
Hippocampus - drug effects
Hippocampus - metabolism
In vivo microdialysis
Male
Microdialysis - methods
Pyrrolidonecarboxylic Acid - analogs & derivatives
Rats
Rats, Sprague-Dawley
Thyrotropin-Releasing Hormone - administration & dosage
Thyrotropin-Releasing Hormone - analogs & derivatives
Thyrotropin-Releasing Hormone - chemistry
TRH analogue
Vertebrates: nervous system and sense organs
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Summary:The centrally active thyrotropin-releasing hormone (TRH) analogue pGlu–Leu–Pro–NH 2 ([Leu 2]TRH) showed a significant increase in the extracellular acetylcholine concentration during its perfusion to the hippocampus in rats, and this effect was manifested upon the delivery of the analogue in much smaller quantities compared to TRH when measured by in vivo intracranial microdialysis. The neuropharmacodynamic efficacy of [Leu 2]TRH upon intravenous administration was augmented by the use of a brain-targeting derivative in which the progenitor sequence of the mature peptide was embedded in a molecular architecture that promoted enhanced brain delivery, retention and in situ generation of the pharmacologically active molecule. Compared to the unmodified peptide, the targeting system significantly improved the cumulative effect of the treatment on extracellular acetylcholine levels in rats.
ISSN:0006-8993
1872-6240
DOI:10.1016/S0006-8993(02)03251-1