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]

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

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)307-314
Number of pages8
JournalPharmacology Biochemistry and Behavior
Volume91
Issue number3
DOIs
StatePublished - Jan 2009

Fingerprint

Serotonin 5-HT2 Receptor Agonists
Pharmacology
2,5-Dimethoxy-4-Methylamphetamine
Serotonin Receptors
Haplorhini
Rats
Neurotransmitter Receptor
Second Messenger Systems
2-(8,9-dihydro-7H-pyrano(2,3-g)indazol-1-yl)-1-methylethylamine
Ion Channels
Chemical elements
Pharmaceutical Preparations
Neurotransmitter Agents
Serotonin
Tissue
Ligands

Keywords

  • 5-HT receptor
  • DOM
  • Drug discrimination
  • MDL 100907
  • Monkey
  • R-DOI
  • Rat

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Pharmacology
  • Toxicology
  • Behavioral Neuroscience
  • Biological Psychiatry

Cite this

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]. / May, Jesse A.; Sharif, Najam A.; Chen, Hwang Hsing; Liao, John C.; Kelly, Curtis R.; Glennon, Richard A.; Young, Richard; Li, Jun Xu; Rice, Kenner C.; France, Charles P.

In: Pharmacology Biochemistry and Behavior, Vol. 91, No. 3, 01.2009, p. 307-314.

Research output: Contribution to journalArticle

May, Jesse A. ; Sharif, Najam A. ; Chen, Hwang Hsing ; Liao, John C. ; Kelly, Curtis R. ; Glennon, Richard A. ; Young, Richard ; Li, Jun Xu ; Rice, Kenner C. ; France, Charles P. / 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]. In: Pharmacology Biochemistry and Behavior. 2009 ; Vol. 91, No. 3. pp. 307-314.
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