Disease relevance of Metkephamide

• Further comparisons of the analgesic and respiratory depressant effects of morphine and two opioid peptides, metkephamid and D-Ala2-D-Leu5-enkephalin, strongly suggest the involvement of mu-2 rather than delta mechanisms in opioid respiratory depression [1].
• This metkephamid-induced Flehmen was preceded by transient bradycardia and apnea followed by somnolence for approximately 1 hour, during which Flehmen was observed intermittently [2].
• Metkephamid, a delta opioid receptor agonist, blocked cold-restraint stress ulcers, reduced absolute ethanol-induced gastric ulcers and, at the lowest and highest doses examined, reduced basal gastric acid secretion in conscious rats, all to a significant degree [3].

High impact information on Metkephamide

• Our results suggest that 140 mg metkephamid compares favorably with 100 mg meperidine for analgesia after episiotomy, but it induces minor side effects more frequently [4].
• Gastrointestinal absorption of peptide drug: quantitative evaluation of the degradation and the permeation of metkephamid in rat small intestine [5].
• The mu-selective peptides D-Ala2-NMePhe4-Gly5(ol)enkephalin, FK 33,824 and morphiceptin, the delta-selective peptides D-Ala2-D-Leu5enkephalin and metkephamid and beta-endorphin (mu- and delta-selective) produced morphine-like stimulus effects after administration into the lateral ventricle [6].
• Previous drug exposure of the cells showed that verapamil, celiprolol, and vinblastine induced the P-gp expression, while metkephamid (MKA) decreased the P-gp expression level as compared to the control [7].
• Four model peptides (Met-enkephalin, [D-Ala2]Met-enkephalin, [D-Ala2]Met-enkephalinamide, and metkephamid) were tested in terms of permeability, lipophilicity, charge, and molecular size [8].

Biological context of Metkephamide

• Colonic absorption and bioavailability of the pentapeptide metkephamid in the rat [9].
• Unlike most enkephalins and opiates, metkephamid binds equipotently to both morphine-selective (mu2) and enkephalin-selective (delta) binding sites [10].
• After intestinal absorption free metkephamid is rapidly hydrolysed on the surface of hepatocytes or endothelial cells, rather than being taken up by hepatocytes [11].

Anatomical context of Metkephamide

• In this study the intestinal degradation and absorption of a synthetic pentapeptide, metkephamid, were investigated in the rat by determination of its wall permeabilities in the small and large intestine and the extent and mechanism of its intestinal degradation [12].
• Concentrations in the hepatic vein were significantly lower than in the portal vein, hepatic extraction ratios were 0.35 +/- 0.14, 0.61 +/- 0.18 and 0.62 +/- 0.28 (SD, n = 4) for 0.1, 0.5 and 1.0 mM metkephamid perfusate concentrations, respectively [9].
• In this study the absorption of the pentapeptide metkephamid following single pass perfusion of rat ascending colon was investigated by monitoring its disappearance from the large intestine and simultaneous appearance in the portal vein, the hepatic vein and the aorta [9].
• Metabolism and transport of the pentapeptide metkephamid by brush-border membrane vesicles of rat intestine [13].
• The fraction of intact metkephamid recovered after single-pass constant perfusion through rat liver reached steady-state very quickly, and it was concluded that metkephamid was hydrolysed enzymatically at the surface of hepatocytes or endothelial cells of microvessels, or both, rather than being taken up by hepatocytes [11].

Associations of Metkephamide with other chemical compounds

• Both treatments took effect within 30 min and peaked at 1 to 2 hr; with 140 mg metkephamid, maximum analgesia was sustained 6 hr, i.e., 2 hr longer than with meperidine [4].
• To elucidate the extent and mechanisms of the first-pass metabolism of peptide drugs in the liver after oral administration, a liver perfusion study was performed in rats using metkephamid, a stable analogue of methionine enkephalin, and thyrotropin-releasing hormone (TRH), as model peptides [11].

Gene context of Metkephamide

• The fraction of metkephamid recovered intact was approximately 40% under protein-free conditions but increased to 70-75% on addition of bovine serum albumin (BSA) to the perfusate [11].

Analytical, diagnostic and therapeutic context of Metkephamide

• The oral administration of metkephamid resulted in undetectable serum levels [14].
• Intravenous injections of high doses of metkephamid (20 and 40 mg/kg) decreased responding by pigeons under a multiple fixed-ratio, fixed-interval schedule of grain presentation [15].

References