Muscarinic antagonists antimuscarinic effects

Dicyclomine (Bentyl), oxybutynin (Ditropan), and tolterodine (Detrol) are nonselective smooth muscle re-laxants that produce relatively little antagonism of muscarinic receptors at therapeutic concentrations. The mechanism of relaxation is not known. Finally, some other classes of drugs can act in part as muscarinic antagonists. For example, the antipsychotics and antidepressants produce antimuscarinic side effects (e.g., dry mouth). 

Muscarinic antagonists have numerous effects on the digestive system (see Chapter 40). The inhibition of salivation by low doses of atropine results in a dry mouth and difficulty in swallowing. Antimuscarinic... 

Answer Antimuscarinics are not frequently used for peptic ulcer disease today because of their many side effects, but they stiU can play a useful role as adjunctive therapy. Unfortunately, high concentrations are required to block gastric acid secretion, which means that many side effects are difficult to avoid. This man works in a dangerous environment, and his concentration cannot be compromised. Although CNS depression and loss of concentration is a concern with tertiary amine muscarinic antagonists, quaternary ammonium muscarinic antagonists... 

Muscarinic antagonists are sometimes called parasympatholytic because they block the effects of parasympathetic autonomic discharge. However, they do not "lyse" parasympathetic nerves, and they have some effects that are not predictable from block of the parasympathetic nervous system. For these reasons, the term "antimuscarinic" is preferable. 

Many antihistamines, antipsychotics and antidepressants have stmctural similarities with muscarinic receptor antagonists and, predictably, show antimuscarinic effects which are considered in many cases the major side effects of these drug categories. Imipramine (Fig. 16.19) is a... 

The antimuscarinic drug atropine, and its derivative ipratropiumbromide, can also be used for antiarrhyth-mic treatment. Muscarinic receptors (M2 subtype) are mainly present in supraventricular tissue and in the AV node. They inhibit adenylylcyclase via G proteins and thereby reduce intracellular cAMP. On the other hand, activation of the M2 receptor leads to opening of hyperpolarizing Ik.acii and inhibits the pacemaker current If probably via the (3y-subunit of the Gi protein associated with this receptor. The results are hyperpolarization and slower spontaneous depolarization. Muscarinic receptor antagonists like atropine lead to increased heart rate and accelerated atrioventricular conduction. There are no or only slight effects on the ventricular electrophysiology. 

Tertiary a-hydroxy acids are key components of a number of muscarinic receptor antagonists, such as oxybutynin (Ditropan as a racemic mixture), which is prescribed for the treatment of urinary incontinence and exhibits classical antimuscarinic side effects, such as dry mouth.88 Because biological results suggested that (.SVoxybutynin displayed an improved therapeutic profile compared to its racemic counterpart, a general and practical entry to optically pure key subunit (S)-90 became of primary importance.89 In their investigations, researchers at Sepracor considered the advantage... 

Acetylcholine antagonists that block the muscarine-like effects, e.g. atropine, are often imprecisely called anticholinergics.The more precise term antimuscarinic is preferred here. 

Atropine is the prototype drug of this group and will be described first. Other named agents will be mentioned only in so far as they differ from atropine. All act as non-selective and competitive antagonists of the various muscarinic receptor subtypes (Ml-3). Atropine is a simple tertiary amine certain others (see Summary) are quaternary nitrogen compounds, a modification that is important as it intensifies antimuscarinic potency in the gut, imparts ganglionblocking effects and reduces CNS penetration. 

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