Neuroendocrine profile of the potential anxiolytic drug S-20499

Eur J Pharmacol. 1995 Feb 14;274(1-3):141-9. doi: 10.1016/0014-2999(94)00719-n.

Abstract

The neuroendocrine profile of the serotonin 5-HT1A receptor agonist and potential anxiolytic drug (+)-4[N-(5-methoxy-chroman-3-yl)N-propylamino]butyl-8-azaspiro-(4, 5)-decane - 7,9-dione (S-20499) was examined in conscious male rats. S-20499 (0.01-20 mg/kg i.p.) dose-dependently elevated plasma adrenocorticotropin (ACTH) and corticosterone concentrations, with maximal effects observed at 15-30 and 30-60 min respectively. S-20499 also reduced plasma prolactin concentration, and did not alter plasma renin activity. S-20499 (1 mg/kg i.p.) also reduced blood pressure and heart rate within 10 min, suggesting reduced sympathetic output. Pretreatment with the 5-HT1A receptor antagonists (-)-pindolol (0.3 mg/kg i.p.) or spiperone (0.01 or 3 mg/kg s.c.) significantly attenuated the stimulatory effects of S-20499 on plasma ACTH and/or corticosterone concentrations. The data suggest that S-20499 stimulates the hypothalamic-pituitary adrenal axis by activating 5-HT1A receptors, although activation of dopamine D2 receptors may contribute to these responses. Like other 5-HT1A receptor agonists, S-20499 does not increase renin secretion. Additionally, it reduces prolactin secretion, presumably by acting as a weak dopamine D2 receptor agonist in the pituitary.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenocorticotropic Hormone / blood*
  • Animals
  • Anti-Anxiety Agents / administration & dosage
  • Anti-Anxiety Agents / pharmacology*
  • Blood Pressure / drug effects
  • Corticosterone / blood*
  • Dopamine Agonists / administration & dosage
  • Dopamine Agonists / pharmacology
  • Dose-Response Relationship, Drug
  • Heart Rate / drug effects
  • Injections, Intraperitoneal
  • Male
  • Neurosecretory Systems / drug effects*
  • Neurosecretory Systems / physiology
  • Pindolol / administration & dosage
  • Pindolol / pharmacology
  • Prolactin / blood
  • Rats
  • Rats, Sprague-Dawley
  • Renin / blood
  • Serotonin Receptor Agonists / administration & dosage
  • Serotonin Receptor Agonists / pharmacology*
  • Spiperone / administration & dosage
  • Spiperone / pharmacology
  • Spiro Compounds / administration & dosage
  • Spiro Compounds / pharmacology*
  • Stereoisomerism

Substances

  • Anti-Anxiety Agents
  • Dopamine Agonists
  • Serotonin Receptor Agonists
  • Spiro Compounds
  • alnespirone
  • Spiperone
  • Adrenocorticotropic Hormone
  • Prolactin
  • Pindolol
  • Renin
  • Corticosterone