Adrenoceptor agonists indirect-acting

Indirect-acting adrenoceptor agonists act only on effector tissues innervated by SANS. 

Indirect-acting adrenoceptor agonists act only on effector tissues innervated by SANS. Denervated effector tissues are nonresponsive because these drugs act to either release transmitter from nerve terminals or to inhibit neurotransmitter reuptake. 

As was noted on p. 68, some agonists, such as amphetamine and tyra-mine, do not act directly on the adrenoceptor. Instead, they exert their effects indirectly on the adrenergic neuron by causing the release of neurotransmitter from storage vesicles. Similarly, some agents act on the adrenergic neuron, to either interfere in neurotransmitter release or alter the uptake of the neurotransmitter into the adrenergic nerve. 

Neurotransmission across adrenergic junctions is mediated by norepinephrine (NE). Adrenergic effectors may act indirectly by influencing NE synthesis, monoamine oxidase (MAO) enzymes, the mobile NE pool, the NE transporter, prejunctional a-adrenoceptors, granule uptake, or release of NE, or they may ad directly on the postjunctional receptor as agonists or antagonists. 

Mode of action Sympathomimetic agonists may directly activate their adrenoceptors, or they may act indirectly to increase the concentration of catecholamine transmitter in the synapse. Amphetamine derivatives and tyramine cause the release of stored catecholamines these sympathomimetics are therefore mainly indirect in their mode of action. Another form of indirect action is seen with cocaine and the tricyclic antidepressants these drugs inhibit reupmke of catecholamines by nerve terminals and thus increase the synaptic activity of released transmitter. 

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