strychnine and Mental-Disorders

From binding studies using 3H-GABA and 3H-strychnine in dissected human brain material, inhibitory amino acid neurotransmitter receptors have a widespread distribution in the human CNS. Generally GABA receptors are predominant in the forebrain and upper brainstem whereas glycine receptors are more localized in the lower brainstem and spinal cord. Some areas (eg. the substantia nigra) have appreciable quantities of both receptors. Although glycine receptors are altered in some pathological conditions (eg. in Parkinson's disease, in the substantia nigra) the neuropharmacology of the glycine system is still poorly understood. On the other hand the GABA system has been intensively studied. Dysfunction of GABA receptors occurs in various neurological states, as epilepsy, Parkinson's disease and Huntington's chorea. Furthermore GABA agonists are active in animal models for dyskinesia, epilepsy and depression, amongst others. Clinical studies with progabide confirm these findings in animal models, and suggest that low-medium affinity GABA agonists are more appropriate clinical agents than are high or very high affinity GABA agonists. From these and many other findings there appears to be a very large potential for creating new pharmacological agents for different neuropsychiatric disorders based on agonist activity at inhibitory amino-acid receptors. From the example of progabide these compounds can be made not only specific for the receptor involved, but also to have a lower incidence of neurotoxic effects than presently available drugs.

Topics: Central Nervous System; Epilepsy; Humans; Huntington Disease; Mental Disorders; Nervous System Diseases; Neurotransmitter Agents; Parkinson Disease; Receptors, Cell Surface; Receptors, GABA-A; Receptors, Glycine; Seizures; Strychnine

Topics: Aminobutyrates; Animals; Choline; Epilepsy; Humans; Hydroxybutyrates; Hypertension; Hypoxia; Mental Disorders; Mice; Nervous System Diseases; Oxygen; Psychopharmacology; Seizures; Sound; Strychnine

Previous work from this laboratory had demonstrated the presence of endogenous morphine, strychnine and nicotine in the mammalian brain and human serum samples. Morphine is synthesised from tyrosine and strychnine and nicotine from tryptophan. This study examines the role of strychnine, nicotine and morphine in neuropsychiatric disorders. The blood levels of tyrosine, tryptophan, strychnine, nicotine and morphine were studied as also RBC membrane Na(+)-K+ ATPase activity. It was found that serum tyrosine levels were reduced and tryptophan levels elevated in all neuropsychiatric disorders studied with a reduction in RBC Na(+)-K+ ATPase activity. Nicotine was present in significant amounts in serum of patients with schizophrenia, CNS glioma and syndrome X with multiple lacunar state. Morphine was present in significant amounts only in the serum of patients with multiple sclerosis and MDP. Strychnine was present in significant amounts in the serum of patients with epilepsy, Parkinson's disease and MDP. The presence of nicotine and strychnine in significant amounts could be related to elevated tryptophan levels suggesting the synthesis of these alkaloids from tryptophan. Morphine was not detected in most of the disorders owing to low tyrosine levels noted in them. Na(+)-K+ ATPase inhibition noticed in most of the disorders could be related to decreased hyperpolarising morphinergic transmission and increased depolarising nicotinergic and strychinergic transmission. The role of morphine, strychnine and nicotine in the pathogenesis of these disorders in the setting of membrane Na(+)-K+ ATPase inhibition is discussed.

Topics: Adult; Alkaloids; Brain Neoplasms; Chromatography, High Pressure Liquid; Erythrocyte Membrane; Glioma; Humans; Male; Mental Disorders; Middle Aged; Morphine; Neoplasm Proteins; Nervous System Diseases; Nicotine; Sodium-Potassium-Exchanging ATPase; Strychnine; Tryptophan; Tyrosine

Topics: Animals; Anticonvulsants; Behavior, Animal; Central Nervous System Diseases; Chlordiazepoxide; Depression, Chemical; Diazepam; Drug Synergism; Electroshock; Emotions; Hexobarbital; Humans; Hypnotics and Sedatives; Mental Disorders; Meprobamate; Mice; Morpholines; Movement; Muscle Relaxants, Central; Neurotic Disorders; Orientation; Oxazepam; Pentylenetetrazole; Rats; Schizophrenia; Strychnine; Tranquilizing Agents

Topics: Alcoholism; Disulfiram; Humans; Magnesium Sulfate; Mental Disorders; Psychoses, Alcoholic; Psychotic Disorders; Strychnine; Tranquilizing Agents

Topics: Alcoholic Neuropathy; Alcoholism; Folic Acid; Humans; Mental Disorders; Neuritis; Psychotherapy; Strophanthins; Strychnine; Vitamin B Complex; Vitamins