Effects of FG 5893, a new compound with 5-HT1A receptor agonistic and 5-HT2 receptor antagonistic properties, on male rat sexual behavior.
In the present study male rat sexual behavior was used to explore the functional properties of FG 5893, a newly developed diphenylbutylpiperazinepyridyl derivative which is a 5-HT1A receptor agonist and a 5-HT2 receptor antagonist. Treatment with FG 5893 (0.1-6.0 mg kg-1) stimulated male rat sexual behavior, as evidenced by a decrease in the number of mounts and intromissions to elicit ejaculation, and a shortening of the ejaculation latency. The stimulatory effects varied in a dose-dependent manner, reaching a maximum at 3.0 mg kg-1. Pretreatment with (+/-)-pindolol (0.5 mg kg-1 -30 min), a selective 5-HT1A receptor antagonist, completely antagonized the stimulatory effects of FG 5893 (1 mg kg-1 -20 min) on male sexual behavior. In addition, the behavioral action of FG 5893 was investigated on various components of the 'serotonin behavior syndrome' including flat body posture, forepaw treading, and lower lip retraction. The effects obtained were compared with those induced by treatment with 8-hydroxy-2(di-n-propyl-amino)tetralin (8-OH-DPAT), the prototype of a 5-HT1A receptor agonist. Compared to 8-OH-DPAT, a 100 times higher dose of FG 5893 (10 mg kg-1) was needed to elicit flat body posture while forepaw treading was never seen. Lower lip retraction was elicited by the lowest doses of FG 5893 (0.1 mg kg-1) and 8-OH-DPAT (0.03 mg kg-1). Treatment with (+/-)-pindolol reduced flat body posture elicited by 8-OH-DPAT and completely eradicated the flat body posture induced by FG 5893.(ABSTRACT TRUNCATED AT 250 WORDS)
Kabi-Pharmacia Therapeutics AB, Malmö, Sweden.
G
G
Andersson
K
K
Larsson
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D004542:Ejaculation / Q000187:drug effects; D005260:Female; D008297:Male; D009539:Nicotinic Acids / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010869:Pindolol / Q000494:pharmacology; D010879:Piperazines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000502:physiology; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D012726:Sexual Behavior, Animal / Q000187:drug effects*
D009539:Nicotinic Acids; D010879:Piperazines; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C081594:FG 5893; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D010869:Pindolol