Sympathetic neurone blocker

An anti-hypertensive sympathetic neurone blocker debrisoquine 27... 

Postganglionic sympathetic neuron blocker enters nerve ending via uptake-] and effects reversed by TCAs, cocaine. Tox severe orthostatic hypotension, sexual dysfunction. 

They block release of noradrenaline at sympathetic nerve endings and therefore cause vasodilation and reduced peripheral vascular resistance. An example of an adrenergic neurone blocker is guanethidine. 

It is, however, interesting to observe that a good number of sympathomimetics in fact do not really mimic the actions of noradrenaline or adrenaline at the effector receptor. They merely induce the release of noradrenaline from the sympathetic postganglionic adrenergic nerves. Such sympathomimetics which exert their action indirectly are comparatively less effective in patients treated with noradrenaline depleting drugs, for instance, the rauwolfia alkaloids, or other adrenergic neuron blockers. 

Hirst Yes, I have. I have stimulated the sympathetic changes with physiological frequencies of stimulation, loaded the animals with benextramine, an irreversible a blocker, and I can see no changes in the neuronal responses although the responses to circulating catecholamines are abolished. 

The basis for the antihypertensive activity of the ganglionic blockers lies in their ability to block transmission through autonomic ganglia (Fig. 20.2C). This action, which results in a decrease in the number of impulses passing down the postganglionic sympathetic (and parasympathetic) nerves, decreases vascular tone, cardiac output, and blood pressure. These drugs prevent the interaction of acetylcholine (the transmitter of the preganglionic autonomic nerves) with the nicotinic receptors on postsynaptic neuronal membranes of both the sympathetic and parasympathetic nervous systems. 

Ganglion blockers competitively block nicotinic cholinoceptors on postganglionic neurons in both sympathetic and parasympathetic ganglia. In addition, these drugs may directly block the nicotinic acetylcholine channel, in the same fashion as neuromuscular nicotinic blockers (see Figure 27-6). 

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