The effect of D-Phenylalanine (D-Phe), a putative carboxypeptidase A inhibitor and its four derivatives (T1-T4) on analgesia, development of tolerance and physical dependence to morphine, and on degradation of both exogenous and endogenous enkephalins was investigated. Systemic administration of either D-Phe or its derivatives produced naloxone-reversible analgesia in the hot-plate test in mice. Naloxone-precipitated morphine withdrawal syndrome was attenuated in mice after systemic subacute administration (7 days, 1.2 mmol/kg, sc) of D-phe derivatives, the development of tolerance to morphine being unchanged. In the presence of either D-Phe or its derivatives in an incubation mixture (up to 10-3 mol/l) the hydrolysis of exogenous 3H-Met5- and 3H-Leu5-enkephalin in striatal homogenates was slightly inhibited. Moreover, the addition of D-Phe or its derivatives seemed to increase the per cent of recovered endogenous Met5-enkephalin released from veratridine-depolarized striatal particles. In contrast, bestatin, an amino-peptidase inhibitor, and a mixture of dipeptides (Tyr-Tyr, Leu-Leu, Leu-Gly) markedly inhibited degradation of both endogenous and exogenous enkephalins in vitro. The results obtained in this study suggest that the pharmacological activity of D-Phe is not directly related to the endogenous opiate system.
|Original language||English (US)|
|Number of pages||9|
|Journal||Polish Journal of Pharmacology and Pharmacy|
|State||Published - Dec 1 1986|
All Science Journal Classification (ASJC) codes
- Pharmaceutical Science