Reserpine, chlorpromazine and other psycholeptic drugs

Reserpine, Chlorpromazine and other Psycholeptic Drugs Reserpine depletes postganglionic sympathetic fibres of their noradrenaline and the peripheral sympathetic responses of animals which have been pretreated with reserpine are those which would be expected to follow loss of sympathetic transmitter . Thus, in adrenalectomized, reserpinized cats, stimulation of the splanchnic nerves does not produce the increase in blood pressure which is seen in non-reserpinized animals. Hexamethonium normally produces hypotension due to ganglionic blockade in the reserpinized animal it is without effect. Reserpine also causes a loss of adrenaline from the adrenal medulla. Since this adrenaline is liberated into the blood stream, it is not surprising that reserpine causes hyperglycaemia. 

Reserpine also causes a loss of noradrenaline from the brain, but it has a similar effect on 5-hydroxytryptamine, dopamine , histamine and GABA . Attempts to determine which, if any, of these substances is most critically concerned in reserpine action have led to conflicting hypotheses which cannot yet be satisfactorily resolved. 

5-hydroxytryptamine accumulates in the brains of animals fed 5-HTP. This accumulation is accentuated in the presence of monoamine oxidase inhibitors and it is accompanied by signs of behavioural stimulation. A similar situation arises if reserpine is administered in conjunction with a monoamine oxidase inhibitor. If 5-hydroxytryptamine is the transmitter substance at the central synapses of the trophotropic system, these results can only be explained on the assumption that the transmitter has reached such a concentration that it is inhibiting the neurones it normally stimulates, resulting in unopposed activity of the stimulant ergotropic system. 

The view that reserpine owes its action to the liberation of 5-hydroxy-tryptamine rather than noradrenaline is based first on the fact that 

5-hydroxytryptamine is more regularly associated with sedation than is noradrenaline release . Reserpine and those of its derivatives that have a tranquillizing action release both 5-hydroxytryptamine and noradrenaline but noradrenaline is also released by substances, such as morphine in the 

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