Pharmacological comparison of the effect of ibogaine and 18-methoxycoronaridine on isolated smooth muscle from the rat and guinea-pig.
M K Mundey, N A Blaylock, R Mason, Stanley D Glick, Isabelle M Maisonneuve, V G Wilson
British Journal of Pharmacology April 1, 2000 DOI: 10.1038/sj.bjp.0703227 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Guinea-pig ileum, rat vas deferens, guinea-pig bladder, rat portal vein |
| Interventions | Ibogaine 18-methoxycoronaridine |
| Topics | Ibogaine |
| Keywords | Smooth muscle Purinergic signaling Pharmacology |
| Citations | 6 |
| Key findings | Ibogaine and 18-methoxycoronaridine enhance purinergic contractions in several smooth muscle preparations without selective interaction with mu-opioid receptors. |
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.