Cholinergic drugs

Drugs affecting the autonomic nervous system (ANS) are divided into two groups according to the type of neuron involved in their mechanism of action. The cholinergic drugs, act on receptors that are activated by acetylcholine (ACh), whereas the adrenergic drugs act on receptors stimulated by norepinephrine or epinephrine. Cholinergic and adrenergic drugs act by either stimulating or blocking receptors of the ANS.

Cholinergic neurons use ACh as a neurotransmitter found in :

1-The preganglionic fibers terminating in the adrenal medulla.
2-The autonomic ganglia (both parasympathetic and sympathetic).
3- The postganglionic fibers of the parasympathetic division.
4-The postganglionic sympathetic division of sweat glands also uses acetylcholine.
5- Cholinergic neurons innervate the muscles of the somatic system and play an important role in the central nervous system (CNS).
Neurotransmission in cholinergic neurons

1. Synthesis of acetylcholine: Choline is transported from the extracellular fluid into the cytoplasm of the cholinergic neuron by an energy-dependent carrier system that co-transports sodium and can be inhibited by the drug Hemicholinium. The uptake of choline is the rate-limiting step in ACh synthesis. Choline acetyltransferase catalyzes the reaction of choline with acetyl coenzyme A (CoA) to form ACh (an ester) in the cytosol.
2. Storage of acetylcholine in vesicles: ACh is packaged and stored into presynaptic vesicles by an active transport process coupled to the efflux of protons. The mature vesicle contains not only ACh but also adenosine triphosphate and proteoglycan.
3. Release of acetylcholine: When an action potential propagated by voltage-sensitive sodium channels arrives at a nerve ending, voltage-sensitive calcium channels on the presynaptic membrane open, causing an increase in the concentration of intracellular calcium. Elevated calcium levels promote the fusion of synaptic vesicles with the cell membrane and the release of their contents into the synaptic space. This release can be blocked by Botulinum toxin. In contrast, the toxin in black widow spider venom causes all the ACh stored in synaptic vesicles to empty into the synaptic gap.
4. Binding to the receptor: ACh released from the synaptic vesicles diffuses across the synaptic space and binds to postsynaptic receptors on the target cell, to presynaptic receptors on the membrane of the neuron that released the ACh, or to other targeted presynaptic receptors.
5. Degradation of acetylcholine: The signal at the post-junctional effector site is rapidly terminated, because acetylcholinesterase (AChE) cleaves ACh to choline and acetate in the synaptic cleft. Pseudocholinesterase, an enzyme found in the plasma, but does not play a significant role in the termination of the effect of ACh in the synapse.
6. Recycling of choline: Choline may be recaptured by a sodium coupled, high-affinity uptake system that transports the molecule back into the neuron.