Use of the pithed rat model to determine the relative potencies of 5-HT2A/2C receptor antagonists following acute intravenous and oral administration.
We investigated the usefulness of the pithed rat model to determine the relative potencies of 5-HT2A/2C receptor antagonists following acute intravenous and oral administration in inhibiting 5-HT-induced pressor responses. The 5-HT2A/2C receptor antagonists, pirenperone, ketanserin, and ritanserin, all dose-dependently inhibited 5-HT-induced pressor responses when administered either intravenously 5 min prior to commencing 5-HT injections or acutely via the oral route 30 min before pithing. All three compounds were found to be of comparable potency in inhibiting 5-HT-induced pressor responses when given i.v. (range of ID50s 3.7-27.5 micrograms/kg), whereas substantial differences became apparent after oral administration (range of ID50s 13.0-214.0 micrograms/kg), as reflected also by the p.o./i.v. ID50 ratios for the drugs. In conclusion, inhibition of 5-HT-induced pressor responses in the pithed rat preparation provides a reproducible and robust procedure in which comparisons can be made of relative potencies of 5-HT2A/2C receptor antagonists, not only by the intravenous route, but also following acute oral administration.
D000284:Administration, Oral; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003655:Decerebrate State / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin