Drug Dependence Liability and Teratogenicity Tests on 2- (2′-Methyl-3′-chloro) anilino-nicotinic acid (Clonixin) in Rhesus Monkeys

Abstract

In the drug dependence liability studies, 4 tests were conducted. In the test on acute CNS effects of the drug, normal monkeys did not show any meaningful or physical changes with single oral doses of the drug at 50, 100, 200, 400, and 500 mg/kg.In the test of substitution of Clonixin for morphine in morphine dependent and withdrawn monkeys, single oral doses of the drug at 20, 50, 100, and 200 mg/kg did not suppress morphine withdrawal signs, and thus did not support physical dependence on morphine.In the physical dependence producing test on Clonixin, repeated oral administration of the drug to naive monkeys at daily doses of 100, 200, and 400 mg/kg for 4 weeks did not produce any physical dependence as observed by naloxone tests.In the intragastric self-administration test in drug seeking behavior conditioned monkeys, Clonixin did not positively reinforce the drug seeking behavior. Thus, Clonixin was found to be dependence free.In the teratogenicity test, 2 pregnant monkeys received 30 mg/kg, 2 other pregnant monkeys received 200 mg/kg, and one pregnant monkey received the vehicle alone, daily by gavage for 7 days, from the 23rd to 29th day of pregancy. All fetuses were removed from the uteruses by cesarean section on 59th, 60th or 61 st day of gestation. Detailed examinations of the fetuses revealed no abnormalities at all in external morphological appearance, visceral organs, or skeletal structures.