Muscarinic acetylcholine receptor antagonism

FIGURE 19-2 Structures of acetylcholine and atropine. Atropine and similar agents antagonize the effects of acetylcholine by blocking muscarinic cholinergic receptors. 

Pharmacology Trospium is an antispasmodic, antimuscarinic agent. Trospium antagonizes the effect of acetylcholine on muscarinic receptors in cholinergically innervated organs. Its parasympatholytic action reduces the tonus of smooth muscle in the bladder. Trospium increases maximum cystometric bladder capacity and volume at first detrusor contraction. 

Muscarinic Receptor Interactions. Excitatory muscarinic effects, such as temporary stimulation of salivation and stimulation of intestinal peristalsis, were seen with 2-PAM. Atropine-like actions were seen at high concentrations (15-20 mg/kg or more), and, when injected rapidly, 2-PAM caused temporary diplopia (nicotinic block) and loss of accommodation in the eye.Both TMB-4 and 2-PAM blocked bradycardia induced by vagal stimulation. At low concentrations, neither compound affected normal intestinal peristalsis, but they did block peristalsis caused by increased vagal stimulation. TMB-4, 2-PAM, and toxogonin antagonized the effect of acetylcholine, acetyl- -methyl-choline, and other agonists on Isolated guinea pig ileum.62... 

Depending on the patient s clinical status, treatment with atropine and pralidoxime may be feasible. Atropine dries secretions and relaxes smooth muscle via antagonism of acetylcholine at its muscarinic receptors. Clinically, this results in decreased sludge and improved ventilation by decreasing bronchoconstric-tion and bronchorrhea. 

The combination possesses antihistamine/deconges-tant/anticholinergic properties. Chorpheniramine competitively antagonizes histamine at Hj-receptor sites phenylephrine stimulates postsynaptic alpha-receptors, resulting in vasoconstriction, which reduces congestion methscopolamine competitively inhibits action of acetylcholine at muscarinic receptors. The combination is indicated for temporary relief of symptoms of allergic rhinitis, casomotor rhinitis, sinusitis, and the common cold. 

Pharmacologic strategy in Parkinson s disease involves attempts to enhance dopamine functions or antagonize acetylcholine at muscarinic receptors. Thus, peripheral side effects must be anticipated. 

A. Anticholinergic agents competitively antagonize the effects of acetylcholine at peripheral muscarinic and central receptors. Exocrine glands, such as those responsible for sweating and salivation, and smooth muscle are mostly affected. The Inhibition of muscarinic activity in the heart leads to a rapid heart beat. 

Although the specificity of receptors is not so strict as that of the most important anabolic and catabolic enzymes, it is at least as strict as the degrad-ative enzymes of microsomes (see Section 3.5). Thus at ganglia, nicotine (but not muscarine) can take the place of acetylcholine, whereas at postganglionic parasympathetic synapses, muscarine (but not nicotine) can take its place (see Table 7.1). Further specificity is shown in acetylcholine antagonism, for which tubocurarine is specific at the neuromuscular junction, hexamethonium at ganglia, and atropine at parasympathetic postganglionic synapses. 

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