The novel 5-HT1A receptor antagonist (S)-UH-301 antagonizes 8-OH-DPAT-induced effects on male as well as female rat copulatory behaviour.
The 5-HT1A receptor agonist 8-hydroxy-2-(dipropylamino)tetralin (8-OH-DPAT) facilitates male rat copulatory behaviour but inhibits female rat copulatory behaviour. The effect of the novel 5-HT1A receptor antagonist (S)-5-fluoro-8-hydroxy-2-(dipropylamino)tetralin [S)-UH-301) on these 8-OH-DPAT-induced responses was tested. 8-OH-DPAT was given s.c. in a dose of 0.176 mumol/kg (50 micrograms/kg). The doses of (S)-UH-301 given s.c. were 1.76 mumol/kg (0.53 mg/kg) and 5.28 mumol/kg (1.60 mg/kg). The administration of (S)-UH-301 10 min before 8-OH-DPAT antagonized the 8-OH-DPAT-induced effects on both male and female rat copulatory behaviour. The results presented strongly support the classification of (S)-UH-301 as a 5-HT1A receptor antagonist. In addition, the effect of the enantiomer of (S)-UH-301, (R)-5-fluoro-8-hydroxy-2-(dipropylamino)tetralin [R)-UH-301), on male rat copulatory behaviour was tested. This enantiomer was found to facilitate male rat copulatory behaviour in a 8-OH-DPAT-like manner, supporting a 5-HT1A agonistic action of (R)-UH-301.
Johansson
C E
CE
Department of Medical Pharmacology, Uppsala University, Sweden.
Meyerson
B J
BJ
Hacksell
U
U
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000031:analogs & derivatives; D000818:Animals; D003307:Copulation / Q000187:drug effects*; D004542:Ejaculation / Q000187:drug effects; D005260:Female; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012702:Serotonin Antagonists; D012726:Sexual Behavior, Animal / Q000187:drug effects; D013764:Tetrahydronaphthalenes / Q000037:antagonists & inhibitors* / Q000494:pharmacology*
D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes; C064282:UH 301; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin