The agonist and antagonist properties of N-allylenkephalins.
The agonist (ID 50) and antagonist (Ke) potencies of the newly synthesized N-allyl derivatives of Met5-enkephalin and Leu5-enkephalin were compared with those of their respective parent compounds on the myenteric plexus-longitudinal muscle preparation of the guinea-pig ileum. N-allyl substitution of the aminenitrogen in the Met5-enkephalin significantly decreased both the ID 50 and the Ke. In contrast, similar substitution in Leu5-enkephalin did not significantly alter the ID50, but caused an almost tenfold increase in the Ke. The results suggest that substitution on the amine-nitrogen of Leu5-enkephalin rather than Met5-enkephalin is more likely to produce potent narcotic antagonists.
D000498:Allyl Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D004723:Endorphins / Q000494:pharmacology*; D004745:Enkephalins / Q000037:antagonists & inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D011957:Receptors, Opioid / Q000187:drug effects*; D013618:Tachyphylaxis
D000498:Allyl Compounds; D004723:Endorphins; D004745:Enkephalins; D011957:Receptors, Opioid; D009270:Naloxone