levorphanol and Heroin-Dependence

According to the hypothesis that the development of physical dependence on and tolerance to opiates depends on the inhibition by opiates of L-asparaginase and L-glutaminase activities in the brain, and the blockade by opiates of the aspartatergic/glutamatergic receptors especially NMDA, four female and fourty-four male heroin addicts were included in a double-blind clinical trial. Four mg chlorpromazine (CPZ) was administered every hour and 10 mg diazepam (DIA) every 6 hours to a group consisting of two female and nineteen male inpatients. The remaining subjects received 15 mg non-opioid antitussive dextromethorphan (DM) instead of CPZ. The withdrawn addicts were controlled twice a day and yawning, lacrimation, rhinorrhoea, perspiration, goose flesh, muscle tremor, dilated pupils, anorexia, joint and muscle aches, restlessness, insomnia, emesis, diarrhea, craving and rejection of smoking as abstinence syndrome signs were observed and rated on a scale of 1, 2 and 3 points according to their intensity. All signs, except perspiration and emesis, were significantly less intense in the group given DM + DIA than CPZ + DIA. The other plus points included the immediate stop of craving and the early onset of smoking in DM + DIA group. The results are considered to be supporting evidence for the hypothesis emphasizing the blockade of NMDA receptors by opiates in opiate addiction. Furthermore, the decrease caused by non-opioid NMDA antagonists in the responsiveness of NMDA receptors appears very promising for the treatment of opiate addicts.

Topics: Adult; Chlorpromazine; Dextromethorphan; Diazepam; Double-Blind Method; Female; Heroin Dependence; Humans; Levorphanol; Male; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome

Stereospecific opiate binding has been demonstrated in human erythrocyte membranes, having a Kd of 9-10(-9) M. In most respects the binding characteristics resemble those of synaptic membranes. These included the correlation of binding affinity and pharmacological potency of opiates; competition by naloxone; inhibition by Ca2+ and Na+; and sensitivity to phospholipases and trypsin. A comparison of stereospecific opiate binding in control human subjects and heroin addicts revealed a 43% increase in the addict group.

Topics: Adult; Brain; Calcium Chloride; Dextrorphan; Erythrocyte Membrane; Erythrocytes; Female; Heroin Dependence; Humans; Hydromorphone; Kinetics; Levorphanol; Male; Morphinans; Phospholipases; Receptors, Opioid; Serine; Sodium Chloride; Stereoisomerism; Structure-Activity Relationship; Synaptic Membranes; Trypsin