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
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.