Letter: Reversal by physostigmine of clozapine-induced delirium.
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Biomedical subjects
Publications and source records attributed to M Karobath.
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Antipsychotic drugs and their clinically impotent congeners were examined as inhibitors of dopamine-sensitive adenylate cyclase (EC 4.6.1.1) in cell-free membrane preparations of the caudate-putamen of rat brain. Of 12 neuroleptic drugs with reported antipsychotic efficacy, all inhibit stimulation of adenylate cyclase by 40 muM dopamine at micromolar concentrations. Among 14 other structurally related drugs that are not clinically effective as antipsychotic agents, 12 were almost ineffective while two drugs were moderate inhibitors of dopamine-sensitive adenylate cyclase.
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Tyrosine hydroxylase activity of synaptosomes isolated from rat brain was examined. A modified tritium-displacement assay was used, which allowed the measurement of tyrosine hydroxylase activity without the addition of either inhibitors of the metabolism of the hydroxylated products or added exogenous cofactor. The enzyme activity was strongly inhibited by the addition of exogenous catecholamines and 3,4-dihydroxy-L-phenyl-alanine. Aromatic amines other than catechols did not markedly influence tyrosine hydroxylase activity. These in vitro findings support the hypothesis that synthesis of catecholamines is regulated by a mechanism of end-product inhibition at the tyrosine hydroxylase step.