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Abstract
The influence of psychotropic drugs on 5-HT metabolism in the brain is reviewed. With neuroleptic drugs, the most significant changes in 5-HT metabolism in the brain are produced by Rauwolfia serpentine alkaloids and benzoquinoline derivatives. Reserpine, deserpidine, rescinnamine, syrosingopine all reduce brain 5-HT levels and a similar reduction is produced by tetrabenazine (Rol-9569) benzquinamide and RO-4 - 1284. B enzoquinolizine derivatives and reserpine interfere with the process of storage of biogenic amines in the presynaptic granules of the brain and peripheral neurons. Other neuroleptics, phenothiazine thioxantene, and butyrophenone derivatives do not affect brain 5-HT levels. Li ions after a short lasting increase in tryptophan uptake into the brain and increase in 5-HT biosynthesis, inducedJthrough a compensatory mechanism an increase in tryptophan hydroxylase. RbCl increases mouse brain 5-HT levels without affecting noradrenaline (NA) or dopamine (DA). Benzodiazepine derivatives, chlordiazopoxide and medazepam, do not change mouse brain 5-HT and 5-HIAA levels but chlordia zepoxide and diazopam inhibit 5-HT turnover in the cortex of rats. Tricyclic antidepressants, desipramine, protriptyline, imipramine and amitriptyline, inhibit NA and 5-HT uptake but do not affect DA uptake. Most MAO inhibitors increase 5-HT content of the different brain regions to a greater extent than NA e.g. iproniazid, tranylcy promine, malamide, phenelzine pargyline, pheniprazine (Catron), phenyli sobutylhydrazine (JB 835j, y -morpholinobutyrophenone, isocarboxazide and clorgyline. Amphetamine does not change brain 5-HT content but releases 5-HT present in brain neurons outside synaptic vesicles especially in the raphe nuclei. Information about the influence of LSD-25 on brain 5-HT are controversial. Mescal“ne, ditran, phencylidine, DOM, psilocybine muscinol and ibotenic acid increase brain 5-HT content but 2-bromolysergic acid and tetrahydrocannabinol do not. mcgPA decreases brain 5-HT and prevents the anesthetic action of hexobarbital and morphine anesthesia. p - Chloroamphetamine and p - chlo ro -N-methylamphetamine lower brain content of 5-HT as does p-acetyldesoxyephedrine (W4010). 5,6-6ibydroxytryptamine induces degeneration of serotonergic neurons. Other drugs affecting 5-HT metabolism include a-methyltyrosine, metaraminol, clonidine, morphine, pentobarbital, fenfluramine and pentylenetetrazol.
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