d-ala(2)-mephe(4)-met(0)-ol-enkephalin and Substance-Withdrawal-Syndrome

Topics: Analgesics; Animals; Brain; Castration; D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; Drug Tolerance; Endorphins; Gonadotropin-Releasing Hormone; Humans; Hypothalamo-Hypophyseal System; Liver; Luteinizing Hormone; Male; Morphine Dependence; Naloxone; Narcotics; Opioid-Related Disorders; Receptors, Opioid; Receptors, Opioid, kappa; Receptors, Opioid, mu; Receptors, sigma; Substance Withdrawal Syndrome; Testis; Testosterone; Time Factors

The effects of 20 mg morphine HCL i.m. and the synthetic metenkephalin analogue FK 33-824 (1.25 mg, i.m.) were compared single blind in 8 addicts undergoing withdrawal from chronic heroin misuse. FK 33-824 was found to reduce withdrawal distress in 6 subjects but was less effective than distress in 6 subjects but was less effective than morphine. The effect of FK 33-824 was described as not morphine-like "an intoxication without euphoria". All 8 subjects preferred morphine to FK 33-824 and five stated that they would refuse to take another dose of FK 33-824. This difference in preference, with regard to the two drugs of substitution, may have been due to side-effects of the enkephalin-like compound: a feeling of oppression in the chest and heaviness in muscles.

Topics: D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; Endorphins; Enkephalin, Methionine; Euphoria; Female; Heroin Dependence; Humans; Male; Morphine; Substance Withdrawal Syndrome

We review the results of more than 120 studies of the treatment of tardive dyskinesia with noncatecholaminergic agents. The disorder is thought to arise from dopamine receptor supersensitivity brought on by long term neuroleptic-induced receptor blockade. Ironically, neuroleptics are the most consistently effective treatment of tardive dyskinesia. Nevertheless, it would be desirable to treat it with other compounds. The most intensively studied drugs are the cholinergics, including physostigmine, deanol, choline, and lecithin, but their efficacy has been equivocal. Anticholinergics, opiates, and tryptophan appear to worsen the syndrome or have no effect. Trials of gamma-aminobutyric acid agonists, lithium, and amantadine also produced mixed results. Effectiveness has been claimed for benzodiazepines, estrogens, and pyridoxine,, but the evidence is scant. A small number of preliminary reports on other treatments are also summarized. We discuss briefly the implications of these studies, but methodological problems limit interpretation.

Topics: Amantadine; Anti-Anxiety Agents; Benzodiazepines; Cyproheptadine; D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; Double-Blind Method; Dyskinesia, Drug-Induced; Enkephalin, Methionine; gamma-Aminobutyric Acid; Humans; Lithium; Parasympathomimetics; Phenytoin; Receptors, Cell Surface; Receptors, Cholinergic; Receptors, GABA-A; Substance Withdrawal Syndrome; Tryptophan