STEREOSELECTIVITY IN CENTRAL ANALGESIC ACTION OF TOCAINIDE AND ITS ANALOGS

被引：10

作者：

FRANCHINI, C ^{[1
]}

NOJA, FC ^{[1
]}

CORBO, F ^{[1
]}

LENTINI, G ^{[1
]}

TORTORELLA, V ^{[1
]}

BARTOLINI, A ^{[1
]}

GHELARDINI, C ^{[1
]}

MATUCCI, R ^{[1
]}

GIOTTI, A ^{[1
]}

机构：

[1] UNIV FLORENCE,DEPT PRECLIN & CLIN PHARMACOL,I-50121 FLORENCE,ITALY

来源：

CHIRALITY | 1993年 / 5卷 / 03期

关键词：

ANTIARRHYTHMIC DRUG; TOCAINIDE; ANTINOCICEPTIVE ACTIVITY; CHIRAL ANALOGS; PRESYNAPTIC RECEPTOR;

D O I：

10.1002/chir.530050306

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The antiarrhythmic drug tocainide (5a) and some related chiral alpha-amino and alpha-imino anilides (5b-e) were synthesized in optically active form. The antinociceptive effects of the different stereoisomers of these compounds were examined and it was found that the analgesic effect of tocainide is due only to its (-)-(R)-enantiomer. Benzyl replacement for methyl group at the stereogenic centre of tocainide causes loss of activity while both enantiomers of the alpha-iminoxilidide 5e and of the strictly related tocainide analog 5d produce an analgesic effect without any stereoselectivity. Pharmacological tests and [H-3] quinuclidinyl benzilate ([H-3]QNB) binding assay, taken together, seem to show that the antinociceptive effect of (-)-(R)-tocainide, like the analgesia induced by lidocaine, procaine, and mexiletine, is due to a central presynaptic cholinergic mechanism of action.

引用

页码：135 / 142

页数：8

共 27 条

[1] TERT-BUTYLOXYCARBONYLAMINO ACIDS AND THEIR USE IN PEPTIDE SYNTHESIS [J].