D-Met2, Pro5-enkephalinamide (DMPEA) is an opioid peptide having analgesic activity in animals more potent after intravenous administration than morphine. It is less toxic but in animals it showed a higher dependence capacity than morphine. Besides analgesia DMPEA produces in rodent behavioral symptoms similar to those evoked by morphine or beta-endorphin, resembling the actions of neuroleptica.
View Article and Find Full Text PDFPsychopharmacology (Berl)
July 1984
The analgesic ED50 values of some classical morphine congeners (morphine, methadone, fentanyl, azidomorphine) in the rat and mouse tail-flick tests were found to be similar. However, several synthetic derivatives of the natural enkephalins were more potent in mice than in rats. (These analogs contain D-amino acid in position 2 and D- or L-sulfonic (or phosphonic) acid residue in position 5).
View Article and Find Full Text PDFSeveral conventionally used in vivo pharmacological assays were applied to examine whether morphine (M) and a potent enkephalin analogue, [D-Met2,Pro5]enkephalinamide (DMPEA) have haloperidol (H)-like neuroleptic activity. The apomorphine (A)-induced stereotypy and the conditioned reflex activity were inhibited by extremely low doses of H, while somewhat higher doses were needed to induce catalepsy or to suppress the A-elicited turning behaviour in rats with unilateral nigral lesion. M produced these effects only in doses higher than needed for analgesia.
View Article and Find Full Text PDFThe opioid activities of enkephalin analogues bearing D- or L-aminopentane-sulfonic/phosphonic acid at position 5 were studied in vitro, in electrically stimulated longitudinal muscle strip of guinea-pig ileum and mouse vas deferens preparations and in vivo in the rat tail-flick test. Using their in vitro effects Met-enkephalin-like, beta-endorphin-like, (nor)morphine-like and derivatives of intermediate character could be differentiated. Correlating the in vitro activities with the analgesic activity in vivo it is concluded that the enkephalin-like character in a pentapetide may hinder the expression of analgesic activity, when the compounds are given into the cerebroventricular system.
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