The Dimensions of Neurology

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Abstract
Advances in neurochemistry and neuropharmacology have enlarged the dimensions of neurology greatly in the last quarter century. An example is seen in the recent chemical and pharmacological inquiry into schizophrenic reactions. A small group of substances of vegetable origin is capable of producing temporary schizophrenic dissociation states in man and animal. These phantastica or hallucinogens are lysergic acid diethylamide (LSD-25), harmine, ibogaine, yohimbine and mescaline. In chemical structure all are indoles or potential indoles. The only exception is cannabis (marijuana), which is a dibenzopyran rather than an indole. Hallucinogens of animal origin are tryptamine, bufotenine and adrenochrome. These, too, are of indolic structure. A 4th, porphobilinogen, is somewhat akin to an indole in structure. The possible relationship of these indoles to clinical schizophrenia provokes an attempt to make a case for metabolic error as an etiology for this disease. Four possibilities exist: (1) tryptamine formation from tryptophan by decarboxylation instead of the normal avenue in the direction of 5-hydroxytryptophan and serotonin, (2) bufotenine formation by double methylation of serotonin rather than its normal oxidation deaminization to 5-hydroxyindoleacetic acid and ultimate catabolism, (3) the abnormal oxidation of epinephrine to adrenochrome rather than its normal catabolism to melanins, etc. A 4th possibility of metabolic error (a more tenuous one) may arise from a disturbance in porphyrin chemistry. The clinician has long suspected that schizophrenia is not a disease entity, but rather a reaction pattern. Perhaps all 4 of these types of metabolic error may be operative; on the other hand none of them may be of etiologic importance. The new ataractic drugs which appear to exert some therapeutic influence in schizophrenia - chlorpromazine, reserpine, and Frenquel - are all inconsistent in their efficacy, which lends credence to the thought that multiple etiologic mechanisms may exist in this disorder. We may expect advances from the chemists and pharmacologists in this field, but they will need the assistance of the clinician along the way. By temperament and training the neurologist is best able to provide this help, and thus to increase the effective dimensions of his own specialty.