Open AccessPharmacological profiles of an anticholinergic agent, phencynonate hydrochloride, and its optical isomers 1
Author(s) -
WANG Liyun,
WANG Yun,
ZHENG Jianquan,
ZHONG Bohua,
He LIU,
Sijian DONG,
RUAN Jinxiu,
LIU Keliang
Publication year - 2005
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2005.00089.x
Subject(s) - chemistry , pharmacology , muscarinic acetylcholine receptor , carbachol , oxotremorine , hydrochloride , endocrinology , receptor , biology , biochemistry
Aim: To comparatively study the pharmacological profiles of 3‐methyl‐3‐azabicyclo (3,3,1)nonanyl‐9‐α‐yl‐α‐cyclopentyl‐α‐phenyl‐α‐glycolate (phencynonate hydrochloride, CPG), an anticholinergic agent, and its enantiomers [ R (–)‐ and S (+)‐CPG]. Methods: The affinity and relative efficacy were tested using radioligand‐binding assay with muscarinic acetylcholine receptors from rat cerebral cortex. The pharmacological activities were assessed in three individual experiments: (1)potentiating the effect of subthreshold hypnotic dose of sodium pentobarbital; (2) inhibiting oxotremorine‐induced salivation; and (3) inhibiting the contractile response to carbachol. Results: The order of potency of phencynonate hydrochloride and its optical isomers to inhibit the binding of [ 3 H]quinucli‐dinyl benzilate ([ 3 H]QNB) was R (–)‐CPG ( K i =46.49±1.27 nmol/L)>CPG ( K i =271.37± 72.30 nmol/L)> S (+)‐CPG ( K i =1263.12±131.64 nmol/L). The results showed that R (–)‐CPG had the highest affinity to central muscarinic receptors among the three compounds, but did not show any central depressant effects at dose from 10.00 to 29.15 mg/kg. CPG increased the effects of subthreshold hypnotic dose of sodium pentobarbital induced‐sleeping [the ED 50 ±95% LC value was 21.06±3.04 mg/kg]. CPG and R (–)‐CPG displayed nearly equipotent effect in depressing oxotremorineinduced salivation [the ED 50 ± 95% LC for R (–) and CPG were 1.10±0.28 and 1.07 ± 0.15 mg/kg, respectively], and the contractile response to carbachol (p A 2 values for R (–) and CPG were 6.84 and 6.80, respectively). S (+)‐CPG presented the lowest anticholinergic profiles, but could potentate effects of its enantiomers in some manner. Conclusions: These data suggested that R (–)‐CPG acted as an eutomer in racemate and a competitive antagonist to acetylcholine muscarinic receptors, but S (+)‐CPG was less active in comparison to R (–)‐CPG and its racemate. The central depressant effects of R (–)‐CPG and S (+)‐CPG were lower in comparison to its racemate.