Smooth muscle relaxants antimuscarinics

A smooth muscle relaxant apparently of the antimuscarinic type whose actions, therefore, are somewhat reminiscent of atropine, is isomylamine (43). Its synthesis begins with the sodamide catalyzed alkylation of cyclohexyl nitrile (40) with l-bromo-3-methylbutane and the resulting nitrile (41) is hydrolyzed to the acid (42) with HBr in acetic acid. Alkylation of the sodium salt of this acid using p-chloroethyldiethylamine leads to the desired 43. 

Nonselective antimuscarinic drugs have been employed in the therapy of peptic ulcers (see Chapter 40) because they can reduce gastric acid secretion they also have been used as adjunctive therapy in the treatment of irritable bowel syndrome. Antimuscarinic drugs can decrease the pain associated with postprandial spasm of intestinal smooth muscle by blocking contractile responses to ACh. Some of the agents used for this disorder have only antimuscarinic activity (e.g., propantheline), while other drugs have additional properties that contribute to their antispasmodic action. Dicyclomine (Bentyl) and oxybutynin (Ditropan) at therapeutic concentrations primarily have a direct smooth muscle relaxant effect with little antimuscarinic action. 

Antispasmodics (see below) are given for abdominal pain, although there is little objective evidence for their efficacy from controlled clinical trials. The generation of evidence is complicated by the variable nature of IBS symptoms, the patients who suffer from them, and the high rate of placebo response in this condition. There are two main classes of antispasmodic, the antimuscarinic drugs and drugs which are direct smooth muscle relaxants. 

Colofac is the proprietary preparation of mebeverine, which is an antispasmodic useful in irritable bowel syndrome. Mebeverine is a direct relaxant of the smooth muscle and, unlike hyoscine, is not an antimuscarinic. 

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). 

The antimuscarinic action of atropine and its analogs relaxes smooth muscle of the ureters and bladder wall and slows voiding (Figure... 

Atropine and other antimuscarinic drugs have been used to provide symptomatic relief in the treatment of urinary urgency caused by minor inflammatory bladder disorders (Table 8-3). However, specific antimicrobial therapy is essential in bacterial cystitis. In the human urinary bladder, M2 and M3 receptors are expressed predominantly with the M3 subtype mediating direct activation of contraction. As in intestinal smooth muscle, the M2 subtype appears to act indirectly by inhibiting relaxation by norepinephrine and epinephrine. 

Short-term relief is thus most effectively achieved by agents that relax airway smooth muscle, of which B-adrenoceptor stimulants (see Chapter 9) are the most effective and most widely used. Theophylline, a methylxanthine drug, and antimuscarinic agents (see Chapter 8) are also used for reversal of airway constriction. 

Dicycloverine and atropine are antimuscarinic drugs included in some indigestion medicines to relieve colic. They exert a relaxant effect on gastrointestinal smooth muscle and inhibit gastric secretion. 

Upon antimuscarinic treatment, smooth muscles of the ureters and bladder wall are relaxed. This leads to urinary retention which is desired for patients with urinary... 

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