SOFT - TIAFT 1998 Scientific Session 1 Wednesday October 7, 1998
Click Picture Carol L. O'Neal, Alphonse Poklis and Aron H. Lichtman*

Department of Pathology, Medical College of Virginia, Richmond, VA, USA
* Department of Pharmacology/ Toxicology, Medical College of Virginia, Richmond, VA, USA

Acetylcodeine (AC) is one of the major impurities of manufacture in heroin. Data on its pharmacology and toxicology is limited and its ability to enhance the pharmacological activity of diacetylmorphine (DIAM) is not known. Acute toxicity, antinociceptive activity and spontaneous locomotor activity studies were conducted with AC and codeine alone and AC in combination with DIAM in male, ICR mice (s.c. injections). In the acute toxicity studies (assessed by convulsant activity) AC and DIAM were found to have similar CD50s of 134 (120-153) and 116 (80-163) umol/Kg, respectively, but the spontaneous clonic-tonic convulsions observed in the AC treated mice were more violent and persisted longer than the DIAM-induced convulsions. Two mice treated with a high dose of AC died within 25 min. following clonic-tonic convulsions whereas all the DIAM treated mice survived 24 hours. No spontaneous convulsions were observed in the codeine treated mice. The CD50 for codeine was 229 (189-278) umol/Kg. When AC was administered in combination with DIAM, the CD50 of DIAM was decreased to 40 (33-47) umol/Kg suggesting that the presence of AC in illicit heroin may increase the toxicity of the drug. AC was found to have a similar analgesic effect as codeine as determined by the tailflick test with ED50s of 36 (31-43) and 52 (40-66) umol/Kg, respectively. In the spontaneous locomotor activity study, AC and codeine were found to have similar activities with ED50s of 34 (26-45) and 30 (20-49) umol/Kg. DIAM was 10-fold more potent in increasing locomotor activity with an ED50 of 3.5 (1.9-6.8) umol/Kg. AC did not alter the locomotor effects of DIAM when given in combination. DIAM was found to have a therapeutic index that was 11-fold and 8-fold greater than the therapeutic index of AC in the tailflick and spontaneous locomotor activity studies, respectively.

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