phosphoramidon and Morphine-Dependence

Enkephalinase inhibitors phosphoramidon, thiorphan or phelorphan suppressed naloxone-precipitated withdrawal symptoms in acute and chronic morphine dependent mice and rats. It is suggested that decreased biotransformation of the endogenous opioid peptides might compensate the relative shortage of exogenous opiates during withdrawal in opiate dependent subjects and could be a new and promising way to attenuate the severity of abstinential syndrome.

Topics: Amino Acids, Sulfur; Animals; Cerebral Ventricles; Cerebrospinal Fluid; Dipeptides; Glycopeptides; Male; Metalloendopeptidases; Mice; Mice, Inbred Strains; Morphine Dependence; Naloxone; Neprilysin; Rats; Rats, Inbred Strains; Stereotyped Behavior; Substance Withdrawal Syndrome; Thiorphan; Tiopronin

The effect of the enkephalinase inhibitor phosphoramidon on the withdrawal syndrome following acute and chronic morphine-induced physical dependence in mice, was investigated. Phosphoramidon administered intracerebroventricularly (50-200 micrograms) suppressed significantly the naloxone-precipitated withdrawal jumping and wet dog shakes while forelimb shakes were potentiated in both acute and chronic morphine-dependent mice. It is suggested that increased saturation of the opioid receptors by endogenous opioid peptides following enkephalinase inhibition, might suppress the severity of the withdrawal syndrome.

Topics: Animals; Behavior, Animal; Endopeptidases; Glycopeptides; Injections, Intraventricular; Male; Mice; Mice, Inbred Strains; Morphine Dependence; Naloxone; Neprilysin; Protease Inhibitors; Substance Withdrawal Syndrome