Add time:08/20/2019         Source:sciencedirect.com

Intracerebroventricular administration of phelorphan (158 nmol/2 μl), a blocker of dipeptidyl-aminopeptidase (enkephalinase B) and other enzymes involved in the enkephalin biodegradation, inhibited in chronic morphine-dependent rats, the occurrence of some of the naloxone-precipitated withdrawal symptoms. This effect of phelorphan was compared with an equimolar dose of the dipeptidyl-car☐y-peptidase inhibitor (enkephalinase A), thiorphan. The results indicate that both drugs decrease some of the naloxone-precipitated withdrawal symptoms (writhing, digging, head hiding, chewing, diarrhoea and Straub tail), while others were potentiated (penile licking) or unaltered (wet dog shakes, grooming and rearing). In addition, phelorphan compared with the controls or thiorphan, pretreated animals, increased the frequency of paw tremor, head shakes, scratching, erection and ejaculation, but other symptoms were decreased (stretching) or unaltered (teeth chattering).The results are discussed in light of the differences in permeability and specificity of the two enkephalinase inhibitors. Furthermore, these data support the hypothesis that the use of enkephalinase inhibitors might be a promising way for the attenuation of the severity of the withdrawal syndrome.

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