The Action of Tranquilizers on Brain Potentials and Serotonin

Abstract

During the past 4 years a number of tranquilizing agents have been used successfully in the treatment of neuroses and psychoses. The most important of these are: chlorpromazine, a phenothiazine derivative prepared as one of a series of antihistaminic and adrenolytic agents; reserpine, an alkaloid originally introduced as a hypotensive agent; benactyzine, a benzilic acid ester with potent anticholinergic action; and meprobamate, a simple propanediol dicarbamate derivative that is devoid of autonomic effects. I t is of interest that compounds so dissimilar in chemical structure and pharmacological action should all be effective as tranquilizers.Brodie and his associates have shown recently that the administration of reserpine markedly decreases the serotonin (5-hydroxytryptamine) levels in the brain (Pletscher, Shore, and Brodie, 1956). They also observed that the excretion of 5-hydroxyindoleacetic acid (5HIAA), a metabolite of serotonin, was markedly increased following the administration of reserpine (Shore, Silver, and Brodie, 1 9 s ) . These investigators postulated a causal connection between the effectiveness of reserpine as a tranquilizer and the liberation of bound serotonin from the brain. I t was therefore of interest to see whether other tranquilizers would also affect serotonin metabolism.Certain tranquilizing agents are known to antagonize serotonin-induced contractions of smooth muscle (Costa, 1956). We have compared the actions of these 4 tranquilizing drugs in their effect on contractions of smooth muscle induced by serotonin and acetylcholine. Chlorpromazine, reserpine, and benactyzine potently antagonized the contractions produced by acetylcholine and serotonin, while meprobamate was ineffective against both stimulants.This report also includes a summary of our studies on the effects of the tranquilizers on the electrical activity of the brain. We have found, in the cat, that meprobamate in low doses synchronizes the electrical activity recorded from the thalamus without causing important changes in other areas of the brain (Hendley, Lynes, and Berger, 1954, 1956. In the present report we have compared meprobamate and other tranquilizers, especially chlorpromazine, in their effect on spontaneous electrical potentials recorded from the cortex and various subcortical structures. Ifffecl of Tranquilizers OPZ Excretioa of 5-Hydroxyindoleacetic AcidJlale rats weighing 200 to 300 gm. were used in this study. Urine samples from 10 animals were pooled in each experiment. Each animal was given 5 ml. of water per 100 gm. body weight to assure a sufficient excretion of urine. Drugs were administered intraperitoneally in the following doses: reserpine 686

The Chemistry and Mode of Action of Tranquilizing Drugs

“…Higher doses of meprobamate protected all animals from strychnine deaths. The effects of various tranquilizers on the electrical activity of the brain have recently been reported by Berger et al (1957). In these experiments recordingswere made in curarized cats and rhesus monkeys using monopolar cortical electrodes and bipolar concentric electrodes for subcortical recordings.…”

Centrally Acting Muscle Relaxants in Tetanus

“…This difference in potency on spinal reflexes has also been observed by Pfeiffer, Riopelle, Smith, Jenney & Williams (1957). Meprobamate has had wide use as a tranquillizing agent, and although it does not produce any marked change in the electroencephalogram it is known to synchronize activity recorded from the thalamus (Berger, Campbell, Hendley, Ludwig & Lynes, 1957;Hendley, Lynes & Berger, 1955). Anderson & Kjaer (1958) and Perlstein (1959) have used it to relieve muscle spasm in human tetanus.…”

Endocrine Management of Selected Cases of Allergy Based on Enzymatic Mechanism of Sensitization

“…8,9 This unique pharmacodynamic action of "autonomie suppressants" has, therefore, been included in the etiological therapy of hypersensitivity states. This suppressive ef¬ fect of tranquilizing agents upon the vagai system via the hypothalamus may not bring any amelioration in allergic states if applied alone, because the hypothalamic pathology of allergic conditions is only a central pro¬ jection of the pathology of a sensitized organ.…”

“…This stage of toxemia can be designated as the "ex¬ trinsic" phase; the acute stage of the ex¬ trinsic phase is known as the constitutional reaction of anaphylactic response (Table 1). Figures 7,8,9,and 10, and the classification of the biochemical and clinical events is presented in Table 1. ) To summarize, the basic mechanism of enzymatic sensitization in allergic reactions is the induction by an antigen of a specific enzyme which is toxic in its action.…”