Cholinergic Pharmacology: Mechanisms and Drug Types

Acetylcholine is the neurotransmitter released from cholinergic or parasympathetic (vagal) nerve fibers at the heart. Cholinergic agonists such as choline esters and anticholinesterases act as parasympathomimetics at the heart to stimulate acetylcholine's action and decrease the force of myocardial contraction (negative inotropism). Increased conduction velocity (or decreased atrioventricular conduction time), as well as increased electrical activity throughout the heart, and at the SA node in particular, are typical cardiac responses resulting from adrenergic stimulation or cholinergic blockade.

Atropine, Ephedrine, and Scopolamine are not cholinomimetic alkaloids as they do not mimic the actions of acetylcholine like Pilocarpine, Muscarine, Nicotine, and Lobeline do.

Diarrhea, salivation, and lacrimation may be seen. Heart rate is usually slowed, and choline esters do not cross the blood brain barrier so delirium is not an adverse effect.

Excessive pilocarpine may initially result in dilation of blood vessels with a drop in blood pressure and a compensatory reflex stimulation of heart rate. Higher levels will directly inhibit heart rate. In addition, pilocarpine stimulation of muscarinic cholinoreceptors can result in miosis, bronchial smooth muscle constriction, and increased GI motility.

The M2 receptor is primarily found in the heart, nerves, and smooth muscle. It is coupled with the G_i/o subtype of G protein and activates the inhibition of cAMP production and the activation of K+ channels.

The Nicotinic Receptor of the muscle type is specifically found at the skeletal muscle neuromuscular junction.

Pilocarpine is classified as an alkaloid cholinoceptor agonist because it acts on cholinergic receptors, leading to constriction of the muscles of the iris and cilia. The incorrect answers provide inaccurate classifications and actions for pilocarpine.

In addition to activating inhibitory G proteins, muscarinic cholinergic agonists stimulate the activity of phospholipase C, increase production of IP3, and increase release of intracellular calcium.

The M3 receptor is predominantly found in glands, smooth muscle, and endothelium. The subtype of G protein involved is Gq/11, and the post-receptor mechanism includes the IP3, DAG cascade.

M5 receptor is primarily found in the Central Nervous System (CNS).

The M4 receptor is predominantly found in the central nervous system (CNS) and signals through G_i/o protein to inhibit cAMP production as the post-receptor mechanism. The incorrect answers provide alternative locations, G protein subtypes, and signaling mechanisms that are not associated with the M4 receptor.

Nicotinic Receptor neuronal type is primarily found in the CNS postganglionic cell body and dendrites. It consists of a pentamer with alpha and beta subunits only and is involved in the Na+, K+ depolarizing ion channel mechanism for post-receptor function.

The M1 receptor is primarily found in nerves, signaling through the Gq/11 subtype of G protein and activating the IP3, DAG cascade as its post-receptor mechanism.