Guanethidine blood-brain barrier

Guanethidine, rarely used as a hypotensive drug, also causes some catecholamine depletion, but unlike reserpine it does not cross the blood-brain barrier and thus has no central sedative effects. It acts selectively because it is taken up into the neuron by the same amine pump that transports the neurotransmitter. 

Guanethidine possesses high af nity for the axolemmal and vesicular amine transporters. It is stored instead of NE, but is unable to mimic functions of the latter. In addition, it stabilizes the axonal membrane, thereby impeding the propagation of impulses into the sympathetic nerve terminals. Storage and release of epinephrine from the adrenal medulla are not affected, owing to the absence of a reuptake process. The drug does not cross the blood-brain barrier. 

Figure 10.19. False transmitters that are used for antihypertensive treatment, a a-Methyldopa passes the blood brain barrier and is decarboxylated to a-methyldopamine, which upon synaptic release stimulates presynaptic 02-receptors. b Guanethidine acts on catecholaminergic synapses in the peripheral autonomous nervous system.

Reserpine and guanethidine are both sympathoplegics that act on the postganglionic sympathetic nerve terminal. Reserpine enters the CNS readily and causes important CNS toxicity. Guanethidine, on the other hand, is too polar to cross the blood-brain barrier easily and is almost devoid of central toxicity. The answer is (D). 

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