Comparative studies of various amphetamine analogues demonstrating different interactions with the metabolism of the catecholamines in the brain

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Abstract

Behavioral studies on the effects of amphetamine, methamphetamine, phenmetrazine, pipradrol, NCA and methylphenidate administered to rats pretreated with reserpine or αmethyltyrosine and additional biochemical analyses demonstrated that all six stimulants affected both brain dopamine and brain noradrenaline metabolism.

The present study permits a distinct separation of these drugs into two groups since the interaction with the catecholamines was found to be mediated by two different mechanism of action: behaviourally, excitation, consisting of locomotor and stereotyped activities after amphetamine, methamphetamine and phenmetrazine, was virtually impossible to inhibit with reserpine even in extremely high doses (50 mg/kg), but was, in contrast, strongly inhibited by α-methyltyrosine. Biochemically, the excitation in reserpinized rats was correlated with the metabolic influence on a reserpine-resistant pool of dopamine.

The very similar behavioural effects produced by pipradrol, NCA, and methylphenidate were in sharp contrast found to be correlated with the influence on a reserpine-sensitive pool of the catecholamines and not with the newly synthesized catecholamines.

Reserpine completely inhibited all behavioural and biochemical effects of pipradrol, NCA and methylphenidate.

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