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]
| Autor: | Jesse A. May, Najam A. Sharif, Hwang-Hsing Chen, John C. Liao, Curtis R. Kelly, Richard A. Glennon, Richard Young, Jun-Xu Li, Kenner C. Rice, Charles P. France |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Male
Agonist Indazoles medicine.drug_class Clinical Biochemistry AL-38022A In Vitro Techniques Pharmacology Toxicology Serotonergic Biochemistry Article Rats Sprague-Dawley Behavioral Neuroscience chemistry.chemical_compound Discrimination Psychological Drug Stability Piperidines Cyclic AMP Receptor Serotonin 5-HT2C medicine Animals Humans Benzopyrans Receptor Serotonin 5-HT2A Calcium Signaling Cloning Molecular Receptor Adrenergic beta-2 Receptor Agonists Biological Psychiatry 5-HT receptor Dose-Response Relationship Drug 2 5-Dimethoxy-4-Methylamphetamine Chemistry Physical Chemistry 5-HT2 receptor Stomach 2 5-Dimethoxy-4-methylamphetamine Macaca mulatta Rats Serotonin Receptor Agonists Fluorobenzenes Serotonin Antagonists Neurotransmitter transport Serotonin 5-HT2 Receptor Agonists |
| Zdroj: | Pharmacology Biochemistry and Behavior. 91:307-314 |
| ISSN: | 0091-3057 |
| DOI: | 10.1016/j.pbb.2008.07.015 |
| Popis: | AL-38022A is a novel synthetic serotonergic (5-HT) ligand that exhibited high affinity for each of the 5-HT2 receptor subtypes (Ki ≤ 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect