Cholinolytic
Anticholinergic, or cholinolytic, agents are substances that weaken, prevent or stop the interaction of acetylcholine with cholinergic receptors. By blocking cholinergic receptors, they act in the opposite way to acetylcholine.
In accordance with the division of cholinergic receptors into m- and n-cholinergic receptors, cholinolytic substances are also divided into substances with a predominant m- or n-cholinolytic effect. This division corresponds to a rather high selectivity of the action of substances of each of these groups. However, it should be borne in mind that to some extent m-cholinolytic substances reduce the reactivity of nicotine-sensitive, and h-cholinolytic substances reduce the reactivity of muscarinosensitive receptors.
Substances with pronounced cholinolytic activity include atropine and related alkaloids (scopolamine, platyphylline, etc.), as well as a number of semi-synthetic and synthetic compounds. Depending on the chemical structure and physico-chemical characteristics, these compounds differ not only in their predominant effect on m- and n-cholinergic receptors, but also in their ability to penetrate the blood-brain barrier and other biological membranes, in duration of action and other properties. This collectively determines the indications for their differentiated use as medicines.
It should be borne in mind that quaternary ammonium compounds (metacin, atrovent, troventol, etc.) poorly penetrate the blood-brain barrier and are used as substances of peripheral cholinolytic action. At the same time, a number of cholinolytics easily penetrate the blood-brain barrier and actively bind to central cholinergic receptors (amisil, antispasmodin, etc.), which served as the basis for combining them into a group of “central cholinolytics”, although to varying degrees they also have a peripheral cholinolytic effect.
Atropine and related alkaloids, as well as a number of synthetic cholinolytic drugs (antispasmodics, aprofen, etc.) have a blocking effect on m-cholinergic receptors (with simultaneous blocking of n-cholinergic receptors). Metacin blocks m-cholinergic receptors more selectively.
In recent years, in connection with the identification of subtypes of m-cholinergic receptors (M1, M2, M3), pharmacological substances that selectively act on these subtypes of receptors have been sought. Such newly developed drugs include pyarentspin (gastrocepin), which selectively blocks M1-cholinergic receptors. A search is underway for drugs that selectively act on other subtypes of m-cholinergic receptors.
n-cholinolytic substances, in accordance with the characteristics of peripheral n-cholinergic receptors, are divided into two groups. Substances that mainly act in the area of ganglion synapses, due to the peculiarities of their action and therapeutic use, are isolated into a special group of “ganglioblocking substances”. Substances acting mainly in the area of somatic neuromuscular synapses are isolated into the group of “curare-like substances”.
According to the predominant effect on the central m- and h-cholinergic receptors, cholinolytic substances can be divided into groups:
– substances with m-cholinolytic activity (scopolamine, amisyl).
– acting mainly on the cholinoreceptors of synapses of the ascending reticular formation and some other subcortical formations of the brain;
– substances with n-cholinolytic activity (antispasmodin, gangleron, etc.), acting mainly in the area of synapses of the cortex and hippocampus;
– substances of a mixed type of action affecting the m- and n-cholinergic systems (aprofen ndr.), which have a blocking effect in the synapses of the cortex and subcortical formations of the brain.
Diphenhydramine is a group of substances that have predominantly central and cholinolytic or mixed effects and have been used in the treatment of Parkinsonism and other diseases of the extrapyramidal system. Some central cholinolytics have found use as tranquilizing drugs (Amisil).
Cholinolytic properties are possessed not only by substances of the listed groups, but also to a certain extent by some antihistamines (diphenhydramine, diprazine, etc.), local anesthetics and other drugs.
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