Pharmacology of the Adrenergic Mechanism
The change of susceptibility to seizures was chosen as a model to investigate transmission mechanisms in the central nervous system. Catecholamine depletors, such as reserpine, prenylamine and guanethidine increase the susceptibility to seizures, given after administration of a monoamineoxidase inhibitor, however, they are anticonvulsive. α-Methyl-m-tyrosine and α-methyl-m-tyramine which decrease brain catecholamine levels did not influence the susceptibility to seizures, possibly these methyl analogues act as false transmitters in this respect. P-Cl-amphetamine inhibited the noradrenaline and dopamine depletion produced by α-methyl-m-tyrosine, but did not change the subcellular distribution of metaraminol. P-Clamphetamine and some other amphetamine derivatives exerted anti-convulsive effect and inhibited the reserpine induced facilitation of convulsions. The anticonvulsive effect of p-Cl-amphetamine seemed to be independent of its serotonin depleting action. Studying the interaction of amphetamine derivatives and catecholamine depletors or receptor inhibitors the results suggested, that the central nervous system excitation and the ability to decrease susceptibility to seizures caused by amphetamine and its derivatives are independent effects. The subcellular distribution of amphetamine and p-Cl-amphetamine showed that this drugs are present in a relatively high concentration in the fraction containing synaptic vesicles. It is suggested that amphetamine and some of its derivatives are able to substitute cerebral catecholamines functionally and some effects of these drugs (e. g. the anticonvulsive effect) may be direct ones.
KeywordsSubcellular Distribution Adrenergic Mechanism Amphetamine Derivative Methyl Analogue Fluorescence Microscopic Study
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