Article date: February 1995
By: Tanja Kimonen, Risto O. Juvonen, Esko Alhava, Markku Pasanen, in Volume 114, Issue 4, pages 832-836
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.
In mouse liver microsomes the IC50 values of pilocarpine were 6 μm for COH and testosterone 15a‐hydroxylase (T15αOH) activities, 4 μm for PROD, ≅ 100 μm for DMNA and testosterone 60‐hydroxylase (T6βOH) activities and > 1 mm for EROD activity.
In human liver microsomes, the IC50 value for COH was 6 μm and for DMNA 10 μm; T15αOH and PROD activities were not detectable but T6βOH and testosterone 16β/2β‐hydroxylase activities were moderately inhibited (IC50 70 μm).
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.
The low IC50 concentrations in vitro indicate potential metabolic interactions between pilocarpine and several P450 enzymes.
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.
In mouse liver microsomes the IC50 values of pilocarpine were 6 μm for COH and testosterone 15a‐hydroxylase (T15αOH) activities, 4 μm for PROD, ≅ 100 μm for DMNA and testosterone 60‐hydroxylase (T6βOH) activities and > 1 mm for EROD activity.
In human liver microsomes, the IC50 value for COH was 6 μm and for DMNA 10 μm; T15αOH and PROD activities were not detectable but T6βOH and testosterone 16β/2β‐hydroxylase activities were moderately inhibited (IC50 70 μm).
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.
The low IC50 concentrations in vitro indicate potential metabolic interactions between pilocarpine and several P450 enzymes.
DOI: 10.1111/j.1476-5381.1995.tb13279.x
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