Morphine-like activity of substituted amides & imides of [D-Ala2, Met5]-enkephalin.
Six enkephalin analogues (N-substituted amides and imides of [D-Ala2, Met5]-enkephalin) were synthesized and tested for opioid activity. All the compounds, except one i.e., compound IV, showed analgesic activity which was much higher than Met-enkephalin and morphine in mice and inhibited electrically induced contractions of isolated guineapig ileum, [D-Ala2, Met5]-enkephalin-morpholide and [D-Ala2, Met5]-enkephalin-beta-Ala-amide were the most potent analgesics and nearly 6 and 500 times as active as morphine and Met-enkephalin respectively. Both the compounds were equipotent on the guineapig ileum preparation, whereas the beta-Ala-amide was about twice as active as the morpholide in the electrically stimulated mouse vas deferens preparation.
Raghubir
R
R
Patnaik
G K
GK
Sharma
S D
SD
Dhotre
B J
BJ
Mathur
K B
KB
Dhawan
B N
BN
D000577:Amides; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives* / Q000494:pharmacology; D007094:Imides; D009020:Morphine / Q000494:pharmacology*; D010147:Pain Measurement; D013329:Structure-Activity Relationship
D000577:Amides; D007094:Imides; D004744:Enkephalin, Methionine; C022118:enkephalinamide-Met, Ala(2)-; D009020:Morphine