Stereochemistry of viminol, a novel central analgesic.
The synthesis of the stereoisomers of the centrally acting analgesic 1-[1-(2-chlorobenzyl)-pyrrol-2-yl]-2-di-sec.-butylamino-ethanol (viminol) is described. Their absolute configuration has been shown by comparing the circular dichroism (CD) curves with those of some phenyl analogs: for one of the viminol stereoisomers the postulated configurational assignment has been recently confirmed by an X-ray analysis. The pharmacological properties shared by the viminol stereoisomers are also described. The R,R configuration of the sec.-butyl groups and the S configuration of the hydroxy group appear to be essential for the agonistic effects: analgesia, tolerance and physical dependence in rodents. The S,R,R configurated viminol does not substitute, however, for morphine in monkeys, using the single dose suppression test. S,S or R,S(S,R) configurations of the sec.-butyl groups are associated with antagonistic properties. The binding capacity of the viminol stereoisomers to the opiate receptors and their influence on the acetylcholine release from the intestinal cholinergic terminals electrically stimulated are also described.
D000701:Analgesics, Opioid; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D004983:Ethanolamines / Q000494:pharmacology; D051379:Mice; D008968:Molecular Conformation; D051381:Rats; D011957:Receptors, Opioid / Q000187:drug effects; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000701:Analgesics, Opioid; D004983:Ethanolamines; D011957:Receptors, Opioid