5.2:
Neurochemical Transmission: Sites of Drug Action
Neurotransmission, the conduction of electrical impulses between neurons, mediates via neurotransmitters.
Autonomic drugs modulate neurotransmission in the autonomic nervous system.
For example, α-methyltyrosine inhibits neurotransmitter biosynthesis, while vesamicol and reserpine prevent its storage in synaptic vesicles.
The arrival of electrical impulses at the presynaptic axonal terminals results in Ca2+ influx and release of neurotransmitters by exocytosis into the synaptic cleft. This process is inhibited by botulinum toxin and guanadrel. However, it is accelerated by latrotoxin and amphetamine.
Released neurotransmitters bind specific receptors on the postsynaptic neuron to produce desired responses.
These receptors can be activated using specific drugs such as nicotine or methacholine, which mimics the neurotransmitters.
The receptors can be blocked by antagonists such as tubocurarine or atropine.
Following transmission, the reuptake of neurotransmitters into the presynaptic neurons is inhibited by drugs such as hemicholinium and cocaine, thereby prolonging neurotransmitter action.
5.2:
Neurochemical Transmission: Sites of Drug Action
Neurochemical transmission, the conduction of electrical impulses between neurons mediated by neurotransmitters, plays a vital role in various physiological processes. Autonomic drugs exert their effects by modulating neurotransmission within the autonomic nervous system. For instance, drugs such as hemicholinium block the precursor uptake necessary for synthesizing acetylcholine, an essential autonomic neurotransmitter. Following synthesis, neurotransmitters are stored in vesicles. Metyrosine and vesamicol inhibit acetylcholine synthesis and its storage in the vesicles. Upon the arrival of an electrical impulse at the axonal terminal, Ca2+ influx occurs, leading to the exocytosis of neurotransmitters, enzymes, and other proteins into the synaptic cleft. Latrotoxins from black widow spider venom promote uncontrolled neuro-exocytosis, whereas botulinum toxin inhibits acetylcholine release.
Following release, neurotransmitters bind to specific receptors on the postjunctional neuron and induce excitatory or inhibitory postsynaptic potential. Nicotine and similar drugs act on the nicotinic receptor as agonists and stimulate the receptor by opening the ion channel in the postsynaptic membrane. In contrast, atropine acts as a muscarinic receptor antagonist and prevents receptor stimulation. Post transmission, neurotransmitters are either taken up by the presynaptic neuron by active reuptake or undergo degradation. For instance, the enzyme acetylcholinesterase degrades acetylcholine into choline and acetate. Norepinephrine transporter reuptakes noradrenaline into the presynaptic neuron. Drugs such as hemicholinium and cocaine block this neuronal reuptake, prolonging neurotransmitter action. Understanding these complex interactions is crucial for developing treatments for neurological disorders and maintaining a healthy nervous system.