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Amelioration of naloxone-precipitated opioid withdrawal symptoms by peripheral administration of the enkephalinase inhibitor acetorphan

Livingston, S. J., Sewell, Robert David Edmunds, Rooney, K. F. and Smith, H. J. 1988. Amelioration of naloxone-precipitated opioid withdrawal symptoms by peripheral administration of the enkephalinase inhibitor acetorphan. Psychopharmacology 94 (4) , pp. 540-544. 10.1007/BF00212852

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Abstract

The effects of 60 min pretreatment with the enkephalinase inhibitor acetorphan were assessed on naloxone-precipitated (2.5 mg/kg IP) abstinence in chronically morphinized rats. In addition, the antinociceptive activity of the compound was investigated in mice. Intraperitoneal injection (50 mg/kg) in rats attenuated some aspects of the opioid withdrawal syndrome such as burrowing, wet dog shakes, squeal on touch hostility, tachypnoea, ptosis and rough hair, whereas jumping and escape behaviour were significantly increased in acetorphan-treated animals. No effect was observed on withdrawal hypothermia or acute weight loss. Similarly, chronic dosing with acetorphan after withdrawal produced no significant effect on body weight. Acetorphan (50 mg/kg IP) failed to produce any antinociceptive activity in the mouse tail immersion test, but potentiated the antinociceptive effect of d-Ala2-d-Leu5-enkephalin. These results are discussed in terms of acetorphan crossing the blood-brain barrier before being hydrolysed to thiorphan, thus yielding opioid withdrawal relieving effects.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Subjects: R Medicine > RS Pharmacy and materia medica
Publisher: Springer-Verlag
ISSN: 1432-2072
Last Modified: 04 Jun 2017 07:57
URI: http://orca-mwe.cf.ac.uk/id/eprint/70455

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