Anticholinergics antispasmodic activity

A great many organic quaternary bases can inhibit the action of acetyl choline in organ systems activated by that neurotransmitter and thus possess anticholinergic-antispasmodic activity. One such agent is methantheline bromide (4), used in the treatment of peptic ulcer and as an antispasmodic agent in intestinal disorders. Its synthesis Involves Friedel-Crafts cyclization of o-... 

Atropine (1) [a racemic mixture of (-i-)-and (-)-hyoscyamine (2)] and scopolamine [(-)-hyoscine] (3) are tropane-type alkaloids found in certain plants in the Solanaceae (nightshade) family nsed medicinally for centuries in Europe, such as Atropa belladonna, Hyos-cyamus niger, and Datura stramonium [7]. The antispasmodic activities of atropine are due to competitive antagonism of acetylcholine at the muscarinic receptor site. Scopolamine is also an anticholinergic agent, and most commonly used for the prevention of nausea and motion... 

Mechanism of Action Competitive inhibitors of the muscarinic actions of acetylcholine, acting at receptors located in exocrine glands, smooth and cardiac muscle, and intramural neurons. Composed of 3 main constituents atropine, scopolamine, and hyoscyamine. Scopolamine exerts greater effects on the CNS, eye, and secretory glands than the constituents atropine and hyoscyamine. Atropine exerts more activity on the heart, intestine, and bronchial muscle and exhibits a more prolonged duration of action compared to scopolamine. Hyoscyamine exerts similar actions to atropine but has more potent central and peripheral nervous system effects. TherapeuticEffect Peripheral anticholinergic and antispasmodic action, mild sedation. Pharmacokinetics None known... 

Another important feature in many of the synthetic anli-chulincrgics used as antispasmodics is that they contain a quaternary nitrogen, presumably to enhance activity. The initial. synthetic quaternary compound mcthantheline bromide has served as a forerunner for many others. Thc.se compounds combine anticholinergic activity of the antimuscar-inic type with some ganglionic blockade to reinfoax the parasympathetic blockade. Formation of a quaternary ammonium moiety, however, introduces the pu.ssibility of blockade of voluntary synapses (curariform activity) this can become evident with sufficiently high doses. 

For their antispasmodic and antisecretory activities in humans, the drugs are administered orally. A comparison of their oral doses (micromoles) indicates that atropine is the most active compound. In clinical experience all three types of anticholinergic activities are exhibited by all compounds. The principal advantage of the available quaternary ammonium compounds lies in the fact that they are elatively free of any of the CNS effects that rm/ be seen with atropine. This may permit the administration of sufficient quantities of the compounds to achieve a more fully effective peripheral anticholinergic action. 

The side effects of these drugs are well known and have been summarized earlier (SED VIII, p. 313). Drugs with selective activity may be classified as antidepressants, antipsychotics, antihistamines, antispasmod-ics or antiparkinsonism agents and yet have anticholinergic actions as side effects. When two or more are given together the unwanted effects are more likely to arise. 

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