(1,2-Diphenylethyl) piperazines as potent opiate-like analgesics; the unusual relationships between stereoselectivity and affinity to opioid receptor.
A series of novel diphenylethylpiperazines were synthesized, and analgesic activities and opioid receptor interactions were evaluated. Analgesic activity of S(+) enantiomer of 1-cyclohexyl analogues (I-C6) was as potent as morphine. This compound showed narcotic properties. Racemate of I-C6 demonstrated the most potent analgesic activities among the enantiomorphic pairs. The R(-) isomer and (-) spa, NN-dimethyl-1, 2-diphenylethylamine, had mu-agonist like character. The S(+) isomer possessed high affinity for all types of the receptor, especially favorable for delta and kappa, in the different manner from opiate-like analgesics. It is conceivable that opioid receptor has various subsites, and this S(+) enantiomer alter the conformation of the receptor.
D000698:Analgesia; D000818:Animals; D001921:Brain / Q000378:metabolism; D051379:Mice; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D010879:Piperazines; D011957:Receptors, Opioid