Cholinergic agonist pilocarpine

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). 

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. 

Other cholinergic agonists have no therapeutic use. Muscarine (4.3) is an alkaloid of the mushroom Anumita muscaria muscarone (4.9) is its semisynthetic analog. Pilocarpine (2.2) is found in the leaves of a shrub and can be used to increase salivation or sweating. Arecoline (4.10) is also an alkaloid, and occurs in the betel nut that is used as a mild euphoriant in India and Southeast Asia. Finally, oxotremorine (4.11) is a synthetic experimental agent that produces tremors and is helpful in the study of antiparkinsonian drugs. 

Berkowitz, A., Sutton, L., Janowsky, D.S., Gillin, J.C. Pilocarpine, an orally active muscarinic cholinergic agonist, induces REM sleep and reduces delta sleep in normal volunteers. Psychiatry Res. 33. 112—119. 1990. 

An alkaloid of natural plant origin, pilocarpine is a direct-acting cholinergic agonist with a dominant action at both peripheral and central muscarinic sites. The cholinomimetic action of pilocarpine on smooth muscle muscarinic receptors generally results in contraction.The response of intraocular smooth muscle to pilocarpine is pupillary constriction, spasm of accommodation, and reduction of lOP. 

Pilocarpine Cholinergic agonist No constriction Constricts an Adie s tonic pupil owing to hypersensitivity... 

Pilocarpine 1% Cholinergic agonist Miosis Fails to constrict a pharmacologically dilated pupil... 

Acetylcholine acts at two different types of cholinergic receptors [see (1) and (2) in Fig. 2.5]. Muscarinic receptors bind ACh as well as other agonists (muscarine, pilocarpine, bethanechol) and antagonists (atropine, scopolamine). There are at least five different types of muscarinic receptors (M1-M5). All have slow response times. They are coupled to G proteins and a variety of second messenger systems. When activated, the final effect can be to open or close channels for K, Ca ", or CL (Bonner, 1989). Nicotinic receptors are less abundant than the muscarinic type in the CNS. They bind ACh as well as agonists such as nicotine or an-... 

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