N-tetrahydrofurfuryl benzomorphans: comparison of a kappa and an agonist/antagonist analgesic.
The N-tetrahydrofurfuryl benzomorphan, MK-2034 is a prototype kappa agonist analgesic. Dehydrogenation and addition of a methyl group into the N-furfuryl side chain (MR-1353) results in a 2-fold decrease in analgesic potency, a 12-fold decrease in affinity for the mu receptor, a 5-fold decrease in affinity for the delta receptor and a 60-fold decrease in affinity for the kappa receptor. Both compounds possess intermediate sodium ratios for 3H-naloxone binding; however, unlike MR-2034, MR-1353 possesses a bell-shaped dose response curve for elevations in striatal dopamine metabolites. These data indicate that MR-1353 is an agonist/antagonist analgesic and suggest that the high kappa affinity of MR-2034 is responsible for the potent analgesia.
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D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001575:Benzomorphans / Q000494:pharmacology*; D003342:Corpus Striatum / Q000032:analysis; D004298:Dopamine / Q000032:analysis; D006719:Homovanillic Acid / Q000032:analysis; D009019:Morphinans / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects*; D017473:Receptors, Opioid, kappa; D013329:Structure-Activity Relationship
D000700:Analgesics; D001575:Benzomorphans; D009019:Morphinans; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D015102:3,4-Dihydroxyphenylacetic Acid; C032478:MR 2034; C045479:MR 1353; D004298:Dopamine; D006719:Homovanillic Acid