Biphasic action of pentazocine in morphine-dependent rats.

Abstract

Abstract-The characteristic actions of pentazocine in morphine-dependent rats were investigated by a drug-admixed food (DAF) method. Pentazocine did not cause evident withdrawal signs when stopped after a continuous administration for 2 months at 3 different dose levels. A state of physical dependency on morphine was produced in rats by feeding them for 3 weeks with food that contained different levels of morphine. Animals exhibiting a moderate degree of morphine-withdrawal signs (17-18 hr after with drawal) received a s.c. cross-administration with pentazocine at 0, 5, 10, 20, 40, 80, and 150 mg/kg. This drug at 20 mg/kg proved most supressive of morphine-withdrawal signs, being about 1 /4 as potent as codeine. In a dose range from 20 to 40 mg/kg, the action of pentazocine on the with drawal signs was reversed, that is, doses not less than 40 mg/kg exerted a dose-related antagonistic action in all the 3 levels of morphine dependent rats. The challenge with levallorphan (2 mg/kg, s.c.) during the chronic application of pentazocine revealed slight withdrawal signs. These findings show that pentazocine has biphasic action on morphine dependence and suggests that this type of drug must have different properties from morphine type drugs.

Substitution and primary dependence studies in animals

“…Similar to the monkeys results, in rats, withdrawal from chronic pentazocine is mild. Unlike monkeys, however, withdrawal in morphine-dependent rats is partially suppressed by pentazocine [21]. The antagonist actions of pentazocine are very weak in the rhesus monkey; however, pentazocine will not antagonize the effect of morphine on schedule-induced responding in monkeys [ 221 and only at very high doses will participate withdrawal in morphine-dependent monkeys [ 71.…”

Efficacy of Full µ-Opioid Receptor Agonists is not Impaired by Concomitant Buprenorphine or Mixed Opioid Agonists/Antagonists – Preclinical and Clinical Evidence

“…The biphasic effect of pentazocine was independent of the degree of morphine dependence. The authors suggest the involvement of receptors other than the MOP receptor, but without further elaborating this explanation [37]. Literature on the clinical use of pentazocine is scarce and does not provide a full insight into the mode of action of pentazocine in humans.…”