The inhibition of CYP enzymes in mouse and human liver by pilocarpine.

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Kimonen T, Juvonen RO, Alhava E, Pasanen M

The inhibition of CYP enzymes in mouse and human liver by pilocarpine.

Br J Pharmacol. 1995 Feb;114(4):832-6.

PubMed ID

7773543 [ View in PubMed

]

Abstract

1. Pilocarpine is a cholinomimetic natural alkaloid. Its interactions with testosterone hydroxylations, coumarin 7-hydroxylase (COH), dimethylnitrosamine N-demethylase (DMNA), pentoxyresorufin O-dealkylase (PROD) and 7-ethoxyresorufin O-deethylase (EROD), which are indicative of the activities of cytochrome P4502A5 (CYP2A5) or 6, 2E1, 2B, 1A, were examined in mouse and human liver microsomes. 2. In mouse liver microsomes the IC50 values of pilocarpine were 6 microM for COH and testosterone 15 alpha-hydroxylase (T15 alpha OH) activities, 4 microM for PROD, approximately 100 microM for DMNA and testosterone 6 beta-hydroxylase (T6 beta OH) activities and > 1 mM for EROD activity. 3. In human liver microsomes, the IC50 value for COH was 6 microM and for DMNA 10 microM; T15 alpha OH and PROD activities were not detectable but T6 beta OH and testosterone 16 beta/2 beta-hydroxylase activities were moderately inhibited (IC50 70 microM). 4. These results suggest that pilocarpine has (i) a high affinity towards phenobarbitone-inducible CYP2A4/5 and CYP2B activities in mouse liver, (ii) a high affinity towards CYP2A6 in human liver microsomes and (iii) a moderate affinity towards CYP3A enzyme(s) in both microsomal preparations. 5. The low IC50 concentrations in vitro indicate potential metabolic interactions between pilocarpine and several P450 enzymes.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Pilocarpine	Cytochrome P450 2A6	Protein	Humans	Unknown	Substrate Inhibitor	Details
Pilocarpine	Cytochrome P450 3A4	Protein	Humans	Unknown	Inhibitor	Details