The opiate agonist activity of enkephalin analogs substituted with different D and L amino acids in position 2 and/or 5 was studied in vitro in longitudinal muscle strip or guinea-pig ileum (GPI), mouse vas deferens (MVD), rabbit's ear artery (REA) and in vivo in 2 analgesic tests. All enkephalin analogs bearing Pro (-OH, -NH2, -NH-Et, -NH-Amyl) in position 5 and also D-Met2, d-Met5-enkephalinethylamide, similarly to β-endorphin were nearly equipotent in GPI and MVD or slightly ( < 5) more potent in MVD whereas those having L-Met, L-Nle or L-Ile at their C terminus were 18 to 300 times more potent in MVD than in GPI. Members of the former group in contrast to the latter were potent analgesics in rats upon intracerebroventricular administration whilst representatives of the latter group were much more potent presynaptic inhibitors in REA preparation than those of the former. Determining the K(e) values of nalrexone against different enkephalin analogs it was found that whilst in GPI naltrexone antagonized the effects of normorphine and all the peptides tested with the same potency, in MVD a rather continuous distribution of K values was found ranging from 0.643 (against normorphine) to 9.210 (against Nle-enkephalin). Calculation of 5pA2 equivalents of naloxone against morphine, β-endorphin and D-met2, Pro5-enkephalinamide indicated identical analgesic receptors for the compounds in the mouse hot plate test but not in rat tail-flick procedure.
|Issue number||suppl. 1|
|Publication status||Published - Jan 1 1978|
ASJC Scopus subject areas