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.
4.3.5.4 Drugs Interfering with Catecholamine Uptake
This group of drugs can also be divided into two categories. The first of these consists
of the false neurotransmitters. Tyramine (4.40), produced by the decarboxylation of
tyrosine (and especially the β-hydroxy derivative of tyramine, octopamine,4.41), can
be taken up through the presynaptic membrane by the rather unselective uptake-1
mechanism. Tyramine then enters the storage granules to a certain extent (even though
the vesicular uptake mechanism is more specific than the presynaptic pump) and dis-
places NE which, when released, causes postsynaptic effects. In addition, tyramine
competes with NE for monoamine oxidase and protects the neurotransmitter from
destruction, thus elevating its actual concentration.
Octopamine (4.41), which carries a β-hydroxyl group, is taken up even more readily
into storage vesicles and is, in turn, released when the neuron fires. As an adrenergic
agonist, octopamine is, however, only about one-tenth as active as NE; therefore, it acts
as a very weak neurotransmitter. Compounds such as this behave like neurotransmitters
of low potency, and are called false transmitters. On the other hand, octopamine may be
a true transmitter in some invertebrates, with receptors that cannot be occupied either
by other catecholamines or by serotonin.
The other group of drugs acting on catecholamine recycling are the true reuptake
inhibitors, which block the amine pump of the reuptake-1 mechanism in central adren-
ergic, dopaminergic, and serotonergic neurons.
NEUROTRANSMITTERS AND THEIR RECEPTORS 227