6.17:
Drugs Affecting Neurotransmitter Release or Uptake
Some drugs that act on the adrenergic neurons can disrupt catecholamine release from synaptic vesicles or interfere with neurotransmitter reuptake.
Reserpine, an alkaloid, blocks the transport of catecholamine into synaptic vesicles, leading to the accumulation of catecholamines in the cytosol. Eventually, they are degraded by MAO, reducing sympathetic transmission.
Guanethidine, a sympatholytic agent, enters the nerve endings and accumulates in synaptic vesicles, displacing noradrenaline. This impedes vesicular exocytosis and neurotransmitter release at the synapse, blocking impulse conduction.
Higher doses of guanethidine can cause structural aberrations in the neuron.
Noradrenaline, when released into the synaptic space, undergoes reuptake via the norepinephrine transporter. Inhibitors of this transporter include serotonin-noradrenaline reuptake inhibitors like duloxetine, tricyclic antidepressants like imipramine, and indirect-acting agonists like cocaine.
Due to their associated side effects, these drugs have limited therapeutic use and have been largely replaced by more selective agents.
6.17:
Drugs Affecting Neurotransmitter Release or Uptake
Certain drugs can affect how neurotransmitters called catecholamines, are released or taken back up in the adrenergic neuron. They can have different effects on the body's sympathetic transmission. Reserpine, a natural compound found in the Rauwolfia shrub, blocks a transporter called vesicular monoamine transporter (VMAT), which leads to a buildup of catecholamines in the cell and reduces sympathetic transmission. Another drug called guanethidine works in multiple ways, including blocking neurotransmitter release and uptake by targeting the catecholamine transporter NET. It can also enter synaptic vesicles and displace noradrenaline. Some other drugs like duloxetine, imipramine, and cocaine also inhibit this transporter. Cocaine, in particular, enhances sympathetic activity by obstructing the reuptake of catecholamines. While these drugs have been studied experimentally, only a few have been used clinically. Newer and more selective drugs have made some of these compounds outdated. However, understanding how these drugs affect the release and reuptake of catecholamines is essential for potential treatments of various disorders.