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Pharmacol Biochem Behav. 2009 Jan;91(3):307-14. doi: 10.1016/j.pbb.2008.07.015. Epub 2008 Jul 30.

Pharmacological properties and discriminative stimulus effects of a novel and selective 5-HT2 receptor agonist AL-38022A [(S)-2-(8,9-dihydro-7H-pyrano[2,3-g]indazol-1-yl)-1-methylethylamine].

Author information

  • 1Ophthalmology Discovery Research, Alcon Research, Ltd., 6201 South Freeway, Fort Worth, Texas 76134, United States. jesse.may@alconlabs.com

Abstract

AL-38022A is a novel synthetic serotonergic (5-HT) ligand that exhibited high affinity for each of the 5-HT2 receptor subtypes (Ki<or=2.2 nM), but a significantly lower (>100-fold less) affinity for other 5-HT receptors. In addition, AL-38022A displayed a very low affinity for a broad array of other receptors, neurotransmitter transport sites, ion channels, and second messenger elements, making it a relatively selective agent. AL-38022A potently stimulated functional responses via native and cloned rat (EC50 range: 1.9-22.5 nM) and human (EC50 range: 0.5-2.2 nM) 5-HT2 receptor subtypes including [Ca2+]i mobilization and tissue contractions with apparently similar potencies and intrinsic activities and was a full agonist at all 5-HT2 receptor subtypes. The CNS activity of AL-38022A was assessed by evaluating its discriminative stimulus effects in both a rat and a monkey drug discrimination paradigm using DOM as the training drug. AL-38022A fully generalized to the DOM stimulus in each of these studies; in monkeys MDL 100907 antagonized both DOM and AL-38022A. The pharmacological profile of AL-38022A suggests that it could be a useful tool in defining 5-HT2 receptor signaling and receptor characterization where 5-HT may function as a neurotransmitter.

PMID:
18718483
[PubMed - indexed for MEDLINE]
PMCID:
PMC3763814
Free PMC Article

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