Antagonism of (+)WAY 100135 to behavioral, hypothermic and corticosterone effects induced by 8-OH-DPAT

Pol J Pharmacol. 1994 Jan-Apr;46(1-2):21-7.

Abstract

The 5-HT1A antagonistic properties of (+)-N-tert-butyl-3-[4-(2-methoxyphenyl)piperazin-1-yl]-2-phenyl pro panamide ((+)WAY 100135) were studied. Its effect on the 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT)-induced behavioral syndrome (flat body posture and reciprocal forepaw treading) in reserpine-pretreated rats, the stimulus effect in a drug discrimination model in rats, the lower lip retraction in rats, the hypothermia in mice and secretion of corticosterone in rats, i.e. responses mediated by 5-HT1A receptors, were examined. (+)WAY 100135 administered in doses up to 10 mg/kg dose-dependently antagonized all the above responses to 8-OH-DPAT, the lowest effective doses ranging from 1.25 to 2.5 mg/kg. At the same time, (+)WAY 100135 alone given in doses of 1.25-10 mg/kg did not mimic the activity of 8-OH-DPAT in the tests used. Our results indicate that (+)WAY 100135 is an antagonist of pre- and postsynaptic 5-HT1A receptors devoid of agonist properties.

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / antagonists & inhibitors*
  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
  • Animals
  • Behavior, Animal / drug effects*
  • Corticosterone / metabolism*
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Hypothermia / chemically induced*
  • Male
  • Mice
  • Piperazines / pharmacology*
  • Rats
  • Rats, Wistar
  • Reserpine / pharmacology
  • Serotonin Antagonists / pharmacology*

Substances

  • Piperazines
  • Serotonin Antagonists
  • WAY 100135
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Reserpine
  • Corticosterone