dextromethorphan and tizanidine

The effects of the opioid agonist dextromethorphan and the alpha 2-adrenoceptor agonist tizanidine on ouabain-induced cardiac arrhythmias were investigated in rats. Ouabain (10 mg/kg i.v.) elicited ventricular arrhythmias in all of the control rats. Administration of dextromethorphan (25 mg/kg i.v.) and tizanidine (0.1 mg/kg i.v.) 30 min before ouabain treatment significantly reduced the incidence of arrhythmias. We suggest that dextromethorphan and tizanidine showed these effects by decreasing excitatory amino acid (EAA) activity. It can be speculated that opioids and other EAA antagonists may have antiarrhythmic actions through both their central and peripheral effects as well.

Topics: Adrenergic alpha-Agonists; Animals; Arrhythmias, Cardiac; Cardiotonic Agents; Clonidine; Dextromethorphan; Excitatory Amino Acid Antagonists; Male; Ouabain; Rats; Rats, Wistar

According to the hypothesis implying that the main mechanism underlying opiate addiction is the blockade by opiates of NMDA receptor functions and subsequent upregulation and supersensitivity of the receptors, noncompetitive NMDA receptor blocker dextromethorphan (DM) has been successfully 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 found responsible for the manifestation of abstinence syndrome signs including craving and neuronal death by excessive stimulation of NMDA receptors, the incomplete blockade of the NMDA receptors minimizes the intensity 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 activity on alpha 2-adrenoreceptors, was combined with DM to obtain further benefits. Forty-four male and three female heroin addicts were the subjects 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 years. Two to three hours after abrupt withdrawal, the outpatients were given 15 mg DM every hour, 25 or 50 mg chlorpromazine (CPZ) + 4 mg TIZ 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 were controlled twice a day. Yawning, rhinorrhea, perspiration, piloerection, restlessness, insomnia, emesis, diarrhea, craving, rejection of smoking and pupils were observed and/or questioned. Two of the 47 outpatients took heroin on the first days.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Ambulatory Care Facilities; Clonidine; Dextromethorphan; Drug Therapy, Combination; Female; Heroin Dependence; Hormones; Humans; Infant, Newborn; Male; Neurotransmitter Agents; Receptors, N-Methyl-D-Aspartate; Substance Withdrawal Syndrome