Acetylcodeine, an impurity of illicitly manufactured heroin, elicits convulsions, antinociception, and locomotor stimulation in mice

Citation
Cl. O'Neal et al., Acetylcodeine, an impurity of illicitly manufactured heroin, elicits convulsions, antinociception, and locomotor stimulation in mice, DRUG AL DEP, 65(1), 2001, pp. 37-43
Citations number
28
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
DRUG AND ALCOHOL DEPENDENCE
ISSN journal
0376-8716 → ACNP
Volume
65
Issue
1
Year of publication
2001
Pages
37 - 43
Database
ISI
SICI code
0376-8716(200112)65:1<37:AAIOIM>2.0.ZU;2-F
Abstract
Acetylcodeine is one of the major impurities present in illicitly manufactu red heroin (diacetylmorphine). Data on its pharmacology and toxicology are limited and its ability to alter the toxic effects of diacetylmorphine is n ot known. The first objective of the present study was to compare the acute pharmacological and toxicological effects of acetylcodeine to those of cod eine and diacetylmorphine in mice by assessing nociception in the tail-flic k test, locomotor stimulation, and convulsive behavior. The second goal of this study was to determine whether acetylcodeine would alter the convulsan t effects of diacetylmorphine. The antinociceptive potencies of acetylcodei ne and codeine were similar. as reflected by their ED50 (95% confidence lim its) values of 35 (29-44) and 51 (40-65) mu mol/kg, respectively. Acetylcod eine was somewhat less potent than codeine in stimulating locomotor behavio r, with ED,, values of 28 (22-37) and 12 (6-24) mu mol/kg, respectively. Di acetylmorphine was considerably more potent than the other two drugs, produ cing antinociception and locomotor stimulation at ED50 values of 2.4 (1.4-4 .1) and 0.65 (0.36-1.2) mu mol/kg, respectively. On the other hand, the con vulsant effects of acetylcodeine (ED50 = 138 (121-157) mu mol/kg) and diace tylmorphine (ED50 = 115 (81-163) mu mol/kg) were similar in potency and bot h were more potent than codeine (ED50 = 231 (188-283) mu mol/kg). Finally, a subthreshold dose of acetyleodeine (72 mu mol/kg) decreased the convulsan t ED50 dose of diacetylmorphine to 40 (32-49). These findings suggest that the convulsant effects of acetyleodeine are more potent than predicted by i ts effects on locomotor activity and antinociception. The observation that acetylcodeine potentiated the convulsant effects of diacetylmorphine sugges ts a mechanism for some of the heroin-related deaths reported in human addi cts. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.