Analgesic potency of S-acetylthiorphan after intravenous administration to mice.
(1993) European Journal of Pharmacology — Vol. 243, n° 2, p. 129-134 (1993)
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- Abstract
- As hydrolysis in serum of acetorphan to acetylthiorphan (N-[(R,S)-3-acetylmercapto-2-benzylpropanoyl]glycine) has been evidenced, both the neutral endopeptidase inhibition in vitro by acetylthiorphan and analgesic potency of acetylthiorphan after intravenous administration to mice in two analgesic models, the hot-plate and the tail-flick tests, were compared with those of thiorphan and acetorphan. Acetylthiorphan showed a decreased degree of neutral endopeptidase inhibition (IC50 = 316 +/- 38 nM) compared to thiorphan (IC50 = 1.8 +/- 0.2 nM). After intravenous administration followed by the hot-plate jump latency test, acetylthiorphan elicited a degree of analgesia equivalent to that with acetorphan but longer lasting. Like acetorphan and thiorphan, acetylthiorphan was devoid of analgesic activity in the tail-flick test. The results indicated that S-acetylation of the thiol function in acetylthiorphan ensures sufficient lipophilicity to permit crossing of the blood-brain barrier and that acetylthiorphan acts via a prodrug mechanism.
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Lambert, D., Mergen, F., Poupaert, J., & Dumont, P. (1993). Analgesic potency of S-acetylthiorphan after intravenous administration to mice. European Journal of Pharmacology, 243(2), 129-134. https://doi.org/10.1016/0014-2999(93)90371-N (Original work published 1993)