Antagonism of (+)WAY 100135 to behavioral, hypothermic and corticosterone effects induced by 8-OH-DPAT.
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.
Przegaliński
E
E
Institute of Pharmacology, Polish Academy of Sciences, Kraków.
Filip
M
M
Budziszewska
B
B
Chojnacka-Wójcik
E
E
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003345:Corticosterone / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007035:Hypothermia / Q000139:chemically induced*; D008297:Male; D051379:Mice; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012110:Reserpine / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*
D010879:Piperazines; D012702:Serotonin Antagonists; C081293:WAY 100135; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D012110:Reserpine; D003345:Corticosterone