Pharmacological comparison of the effect of ibogaine and 18-methoxycoronaridine on isolated smooth muscle from the rat and guinea-pig.

Ibogaine and 18-methoxycoronaridine, alkaloids with reported anti-addictive properties, modulated electrically-evoked contractions in smooth muscle preparations but did not selectively interact with mu-opioid receptors. In guinea-pig ileum, both drugs concentration-dependently inhibited cholinergic contractions (ibogaine pIC50 5.28, 18-methoxycoronaridine pIC50 5.05), an effect not blocked by naloxone. In rat vas deferens, they enhanced purinergic contractions and caused a 3- to 5-fold rightward shift of DAMGO-induced inhibition. In guinea-pig bladder, both drugs doubled the purinergic component of neurogenic contractions without affecting cholinergic contractions. Ibogaine, but not 18-methoxycoronaridine, enhanced spontaneous contractions of rat portal vein. The pronounced enhancement of purinergic contractions is a novel finding warranting further investigation.

Study at a glance

Abstract

Ibogaine and 18-methoxycoronaridine are naturally occurring alkaloids reported to possess antiaddictive properties in several models of drug dependence. We have examined their effect at mu-opioid receptors regulating neurogenic contractions of several smooth muscle preparations and also against spontaneous contractions of the rat isolated portal vein. Ibogaine (pIC(50) 5.28) and 18-methoxycoronaridine (pIC(50) 5.05) caused a concentration-dependent inhibition of cholinergic contractions of the guinea-pig ileum which was not affected by the opioid receptor antagonist naloxone (1 microM). In the rat isolated vas deferens ibogaine and 18-methoxycoronaridine caused a concentration-dependent enhancement of purinergic contractions. Both agents (30 microM) caused a 3 - 5 fold rightward displacement of DAMGO-induced inhibition of purinergic contractions, but similar effects were observed for ibogaine against alpha(2)-adrenoceptor-mediated inhibition of neurogenic responses. In the guinea-pig isolated bladder both ibogaine (10 microM) and 18-methoxycoronaridine (10 microM) caused a 2 fold increase in the purinergic component of neurogenic contractions without significantly altering cholinergic contractions or responses to exogenous ATP. In contrast, ibogaine (1 - 30 microM), but not 18-methoxycoronaridine, caused a concentration-dependent enhancement of spontaneous contractions of the rat isolated portal vein. In summary, while ibogaine and 18-methoxycoronaridine modulated electrically-evoked contractions in the three preparations examined, we have no evidence for a selective interaction with pre-junctional mu-opioid receptors. The pronounced enhancement of purinergic contractions produced by both agents is a novel finding and worthy of further investigation.