Behavioral effects of phenylpiperidine narcotic antagonists

The effects of three phenylpiperidines were studied in pigeons responding under a multiple fixed-ratio 30-response, fixed-interval 5-minute schedule of grain presentation. The first one studied was LY-27372 which as narcotic agonist analgesic effects but not antagonist activity. It decreased responding in both components and was not antagonized by naloxone. The two other drugs, LY-88329 and LY-99335, are tri-alkyl-4-phenylpiperidines which have narcotic antagonist activity. They decreased responding at doses of 5 and 40 mg/kg, respectively, when administered alone. When administered in combination with 20 mg/kg of morphine, they antagonized morphine's effects at 0.16 and 0.08 mg/kg respectively. A 10 mg/kg dose of pentobarbital attenuated the behavioral suppressant effects of 40 mg/kg of LY-99335, but not the suppressant effects of 5 mg/kg of LY-88329 or of 10 mg/kg of LY-27372. The data show that LY-99335 has a large separation between the doses which antagonized morphine and those which alone produce behavioral suppression by a proconvulsant effect at higher doses.