Binding of psychoactive drugs to rat brain amine receptors, measured ex vivo, and their effects on the metabolism of biogenic amines

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Abstract
Ex vivo receptor binding experiments and measurements of the concentrations of the amine metabolites HVA, MOPEG-SO4 and 5-HIAA were carried out on rat brain tissues to analyse the effects of several neuroleptics (haloperidol, chlorpromazine, thioridazine, clozapine, fluperlapine), antidepressants (amitriptyline, mianserin, zimelidine) and other drugs (pizotifen, ketanserin, prazosin) on brain aminergic systems. It was found that in all cases where drugs reduced 3H-haloperidol binding to striatal D2-receptors ex vivo (haloperidol, chlorpromazine, thioridazine, clozapine, fluperlapine, pizotifen, zimelidine), the same drugs caused a pronounced increase, in vivo, in the striatal HVA-concentration, i.e. an increase in DA-turnover. The HVA-increase was directly proportional to the extent of the reduction of 3H-haloperidol binding. These findings suggested that in the 3H-haloperidol assay binding of drugs is to functional D2-receptors regulating the release of DA. In contrast, reduction of binding of 3H-prazosin to brain stem α1-receptors ex vivo (all drugs except zimelidine) was only associated with an in vivo increase in the MOPEG-SO4 concentration in some cases (haloperidol, chlorpromazine, thioridazine, clozapine, fluperlapine, ketanserine). Similarly, reduction of 3H-spiperone binding to 5-HT2-receptors in the frontal cortex (all agents except prazosin and zimelidine) was only associated with an increase in the 5-HIAA concentration in certain cases (thioridazine, clozapine, fluperlapine, pizotifen, ketanserin). The present data indicate that in the brain α1- and 5-HT2-receptors do not seem to be linked directly to the processes which govern the turnover of the neurotransmitters DA, NA or 5-HT. These studies show that the ex vivo receptor binding technique can be useful for measuring the presence of systemically administered drugs in the brain and, particularly when combined with other biochemical measurements, for investigating the role of different transmitter systems in the regulation of physiological processes in the brain.

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