The hallucinogenic herb Salvia divinorum and its active ingredient salvinorin A inhibit enteric cholinergic transmission in the guinea-pig ileum.
Salvia divinorum is a widespread hallucinogenic herb traditionally employed for divination, as well as a medicament for several disorders including disturbances of gastrointestinal motility. In the present study we evaluated the effect of a standardized extract from the leaves of S. divinorum (SDE) on enteric cholinergic transmission in the guinea-pig ileum. SDE reduced electrically evoked contractions without modifying the contractions elicited by exogenous acetylcholine, thus suggesting a prejunctional site of action. The inhibitory effect of SDE on twitch response was abolished by the opioid receptor antagonist naloxone and by the kappa-opioid antagonist nor-binaltorphimine, but not by naltrindole (a delta-opioid receptor antagonist), CTOP (a mu-opioid receptor antagonist), thioperamide (a H(3) receptor antagonist), yohimbine (an alpha(2)-receptor antagonist), methysergide (a 5-hydroxytryptamine receptor antagonist), N(G)-nitro-L-arginine methyl ester (an inhibitor of NO synthase) or apamin (a blocker of Ca(2+)-activated K(+) channels). Salvinorin A, the main active ingredient of S. divinorum, inhibited in a nor-binaltorphimine- and naloxone-sensitive manner electrically induced contractions. It is concluded that SDE depressed enteric cholinergic transmission likely through activation of kappa-opioid receptors and this may provide the pharmacological basis underlying its traditional antidiarrhoeal use. Salvinorin A might be the chemical ingredient responsible for this activity.
Capasso
R
R
Department of Experimental Pharmacology, University of Naples Federico II, Naples, Italy. rafcapas@unina.it
Borrelli
F
F
Capasso
F
F
Siebert
D J
DJ
Stewart
D J
DJ
Zjawiony
J K
JK
Izzo
A A
AA
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D004224:Diterpenes / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D045785:Diterpenes, Clerodane; D004347:Drug Interactions; D004558:Electric Stimulation; D017615:Enteric Nervous System / Q000187:drug effects* / Q000502:physiology; D006168:Guinea Pigs; D006213:Hallucinogens / Q000494:pharmacology*; D007082:Ileum / Q000187:drug effects* / Q000294:innervation* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009197:Myenteric Plexus / Q000187:drug effects; D010275:Parasympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D010936:Plant Extracts / Q000494:pharmacology; D027544:Salvia / Q000737:chemistry*; D013268:Stimulation, Chemical; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology
D004224:Diterpenes; D045785:Diterpenes, Clerodane; D006213:Hallucinogens; D010936:Plant Extracts; D000109:Acetylcholine; C090499:salvinorin A