THE COMBINATION OF TIZANIDINE MARKEDLY IMPROVES THE TREATMENT WITH DEXTROMETHORPHAN OF HEROIN ADDICTED OUTPATIENTS

According to the hypothesis implying that the main mechanism underlyin g opiate addiction is the blockade by opiates of NMDA receptor functio ns and subsequent upregulation and supersensitivity of the receptors, noncompetitive NMDA receptor blocker dextromethorphan (DM) has been su ccessfully used in the heroin addict treatment. As the stimulation of NMDA receptors modulates the release of neurotransmitters and hormones such as NE, D, ACh, GH, LH, LSH, ACTH etc., all of which have been fo und responsible for the manifestation of abstinence syndrome signs inc luding craving and neuronal death by excessive stimulation of NMDA rec eptors, the incomplete blockade of the NMDA receptors minimizes the in tensity of the abstinence syndrome and provides the downregulation of the receptors. In the present study, tizanidine (TIZ), which inhibits the release of endogenous excitatory aminoacids by the agonistic activ ity on alpha(2)-adrenoreceptors, was combined with DM to obtain furthe r benefits. Forty-four male and three female heroin addicts were the s ubjects of the study. Their daily mean heroin intake was about 2.28 g street heroin. The main duration of heroin use was approximately 3.4 y ears. Two to three hours after abrupt withdrawal, the outpatients were given 15 mg DM every hour, 25 or 50 mg chlorpromazine (CPZ) + 4 mg TI Z every six hours and 10 mg diazepam + 10 mg hyoscine N-butyl Br + 250 mg dipyrone every six hours three hours following CPZ. The addicts we re controlled twice a day. Yawning, rhinorrhea, perspiration, piloerec tion, restlessness, insomnia, emesis, diarrhea, craving, rejection of smoking and pupils were observed and/or questioned. Two of the 47 outp atients took heroin on the first days. The others were heroin-free at least throughout the treatment period of eight days. A shorter-lasting abstinence syndrome with considerably less intense signs was observed . Craving, insomnia, emesis, diarrhea, restlessness, rejection of smok ing appeared markedly attenuated. Since TIZ binds to the imidazoline r eceptor with approximately 20 times higher affinity than the alpha(2)- adrenoreceptors, TIZ may attenuate intensity of opiate abstinence synd rome via I-1 imidazoline-receptors.