Elsevier

Life Sciences

Volume 23, Issue 2, 10 July 1978, Pages 99-104
Life Sciences

Enhanced analgesic activity of D-Ala2 enkephalinamides following D-isomer substitutions at position five

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Abstract

The analgesic potency of D-Ala2, Met5- and D-Ala2, Leu5-enkephalinamide was increased following substitution of the D-isomers at position five. The substituted analogs were 2.5 times as potent as morphine in producing analgesia in rats when administered intraventricularly and 0.2 as potent as morphine when administered intravenously. D-Ala2, D-Leu5-enkephalinamide produced naloxone-reversible analgesia by the intravenous route in monkeys. The enhanced systemic activity following D-isomer substitutions at position five appeared to be due to some factor other than increased stability to peptidase degradation at the C-terminus.

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