Cholinergic agonist

A significant age-related decrease in the density of muscarinic acetylcholine receptors was observed on membranes of guinea-pig lungs dissected free of large vessels and bronchi (Suzuki et al. 1985). 

In the foetal rabbit lung, pilocarpine administered subcutaneously to the mother (5 mg/kg) on days 24 through 27 of gestation, morphometry revealed a significant increase in the number of mature type II cells, both per unit area and per 1,000 lung cells of any kind (Smith et al. 1979). By electron microscopy, the alveolar epitheUum demonstrated mor- 

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Initial attempts to treat AD using direct cholinergic agonists were limited by low efficacy and side-effect issues (140—142). Thus trials using RS-86 (25), oxotremorine [70-22-4] (26), arecoline [63-75-2] (27), and pilocarpine [92-32-7] (28) to treat AD were equivocal (Eig. 5). However, the identification of multiple subtypes of muscarinic receptors has stimulated a search for subtype specific muscarinic agonists which may limit side effects while increasing efficacy. 

A special feature of the iris is its autonomic innervation. Sympathetic activation widens the aperture of the iris whereas impulses from the parasympa thetic nervous system decrease the aperture size. Therefore adrenergic agonists and anticholinergic compounds both increase the aperture of the iris, i.e., cause mydriasis, and antiadrenergic and cholinergic agonists decrease it, i.e., cause miosis. The iris can thus be considered an excellent mirror reflecting the balance of the autonomic nervous system in the body. " ... 

When Hie cholinesterase inhibitors are administered with the anticholinergic drugp, there is a potential decrease in activity of the anticholinergic drug. There is an increased risk of toxicity of theophylline when the cholinesterase inhibitors are administered with tacrine There is a synergistic effect when tacrine is administered with succinyl-choline, cholinesterase inhibitors, or cholinergic agonists (eg, bethanechol). 

The oral cholinergic agonists pilocarpine and cevimeline are used for patients with combined dry eye and dry mouth (e.g., Sjogren s syndrome) or severe dry eye. By binding to muscarinic receptors, the cholinergic agonists may increase tear production. Excessive sweating is a common side effect with pilocarpine and may limit its use (Table 60-10). 

Pontine cholinergic agonists and acetylcholine esterase inhibitors... 

N-methylscopolamine (Costa et al. 1982b Schwab et al. 1983). Animals made tolerant to disulfoton were resistant to the lethal or adverse effects of cholinergic agonists, such as carbachol (Brodeur and DuBois 1964 Costa et al. 1981 Schwab and Murphy 1981) and oxotremorine (Costa et al. 1982b McPhillips 1969a), which are not hydrolyzed by acetylcholinesterase. Tissues from animals tolerant to disulfoton such as the ilea (Foley and McPhillips 1973 McPhillips 1969b McPhillips and Dar 1967) and the atria (Perrine and McPhillips 1970 Schwab et al. 1983), were resistant to the effects of carbachol and/or oxotremorine. Because the uterus and vas deferens have a relatively sparse parasympathetic innervation compared to the ileum and do not receive a steady flow of impulses via this system, these tissues were not as subsensitive to carbachol as the ileum (Foley and McPhillips 1973). Thus, acetylcholine accumulation may be a prerequisite for tolerance development. 

Raffaele KC, Berardi A, Asthana S, Morris P, Haxby JV, Soncrant TT. (1991). Effects of long-term continuous infusion of the muscarinic cholinergic agonist arecoline on verbal memory in dementia of the Alzheimer type. Psychopharmacol Bull. 27(3) 315-19. 

Raffaele KC, Asthana S, Berardi A, Haxby JV, Morris PP, Schapiro MB, SoncrantTT. (1996). Differential response to the cholinergic agonist arecoline among different cognitive modalities in Alzheimer s disease. Neuropsychopharmacology. 15(2) 163-70. 

Griinhagen HH, Iwatsubo M, Changeux JP. 1977. Fast kinetic studies on the interaction of cholinergic agonists with the membrane-bound acetylcholine receptor from Torpedo marmorata as revealed by quinacrine fluorescence. Fur J Biochem 80 225-242. 

Psychiatric disorder Cholinergic agonists may have dose-related CNS effects. Consider this when treating patients with underlying cognitive or psychiatric disturbances. 

Mecfianism of Action A cholinergic agonist that binds to muscarinic receptors of effector cells, thereby increasing secretion of exocrine glands, such as salivary glands. Therapeutic Effect Relieves dry mouth. 

Wilens, T.E., Biederman, J., Spencer, T.I. Bostic, J., Prince, J., Mon-uteaux, M.C. Soriano, J., Fine, C., Abrams, A., Rater, M., and Polisner, D. (1999a) A pilot controlled clinical trial of ABT-418, a cholinergic agonist, in the treatment of adults with attention deficit hyperactivity disotdet. Am J Psychiatry 156 1931-1937. 

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