Pilocarpine pharmacology

The most frequent adverse experiences associated with pilocarpine were a consequence of the expected pharmacologic effects. Adverse reactions occurring in at least 3% of patients include the following Sweating, nausea, rhinitis, chills, flushing, urinary frequency, dizziness, asthenia, headache, dyspepsia, lacrimation, diarrhea, edema, abdominal pain, amblyopia, vomiting, pharyngitis, and hypertension. 

An example of a degradable matrix system is the pilocarpine-containing inserts formulated by Saettone et al. [148]. Pilocarpine nitrate and polyacrylic acid were incorporated into a matrix containing polyvinyl alcohol and two types of hydroxy-propyl methylcellulose. It was shown that all inserts significantly increased the pharmacological effect (miotic response) compared to a solution of pilocarpine nitrate. 

The kinetics of the hydroxide ion-catalyzed epimerization of pilocarpine to isopilocarpine and of its hydrolysis to pilocarpic acid have been studied (56). Both forms of degradation lead to loss of pharmacological activity. The importance of possible inactivation by epimerization during thermal sterilization of ophthalmic preparations of pilocarpine was pointed out. It was also considered that some epimerization would always occur during the extraction of pilocarpine from Jaborandi leaves, and that isopilocarpine might, therefore, be an artifact and not a genuine plant alkaloid (55). 

Although the pharmacological properties of pilocarpine have been studied extensively (106), little is known of the structural requirements for its parasympathomimetic activity. In 1982 Aboul-Enein and Al-Badr published an extensive review on the structure-activity relationship of compounds that are structurally related to pilocarpine (102) this review also gives a prognosis of receptor sites. A general conclusion is that any slight structural modification of the pilocarpine molecule causes a drastic reduction in or complete loss of its biological activity. 

Metapilocarpine was first reported by Pinner he obtained it by heating pilocarpine hydrochloride at 225-235°C (118). Polonovski proposed a betaine structure (58) for the compound (119). On reinvestigation, metapilocarpine was shown to be a racemic mixture of isopilocarpine (120). The structure was proved by spectral analysis and by GLC comparison with authentic isopilocarpine. The pharmacological activity of the racemic product was compared to that of (+)-pilocarpine and (+)-isopilocarpine (120). 

In 1973 Koda el al. 122) exposed pilocarpine to aminolysis and lithium aluminum hydride reduction, and then obtained several analogs. Treatment with ammonia or with aqueous methylamine or isopropylamine at room temperature gave the hydroxy amides 64-66. Reaction of pilocarpine with ammonia at 200-210°C yielded a lactam, the pilocarpine analog 67. Similarly, the /V-methyllactam 68 was prepared by reaction with liquid methylamine at 225°C. Reduction of pilocarpine with lithium aluminum hydride (LAH) in tetrahydrofuran yielded the tetrahydrofuran analog 69. Preliminary pharmacological studies indicated interesting cholinergic activity. 

Q3 Outline the pharmacological properties of the cholinergic agent pilocarpine and its action on sweat glands in the skin. 

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

A general review on the use of electrochemical methods for the synthesis of N-heterocycles and natural products includes a section on imidazole derivatives. Thin-layer chromatographic methods for the separation of imidazole alkaloids have been briefly reviewed. Pharmacological effects of pilocarpine (15) have been summarized as part of an excellent review on convulsant alkaloids. ... 

V -rrans-Cinnamoylhistamine (16) has been identified in Acacia spirorbis The alkaloid referred to as metapilocarpine has been shown to be identical with ( )-isopilocarpine (17). Its pharmacological effects were found to be similar to that of pilocarpine (15). 

Analog (130), having the same substitution pattern as pilocarpine,was equipotent to pilocarpine in a guinea pig ileum assay. In vitro base-catalyzed epimerization of pilocarpine at the C-ethyl group position forms the diaste-reomer isopilocarpine in which pharmacologic activity is lost (171). 

Pilocarpine is widely used in ophtalmology in eye-drops. However, in solution it may undergo epimerization to isopilocarpine, and even hydrolysis to pilocarpic acid. In both cases loss of pharmacological activity is the result. Therefore, the analysis of ophtalmic solutions for pilocarpine and its decomposition products have been the subject of several investigations. 

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