The influence of anticholinergic drug selection on the efficacy of antidotal treatment of soman-poisoned rats

被引:17
作者
Kassa, J [1 ]
Fusek, J [1 ]
机构
[1] Purkyne Mil Med Acad, Hradec Kralove 50001, Czech Republic
关键词
soman; atropine; benactyzine; biperiden; scopolamine; HI-6; rat;
D O I
10.1016/S0300-483X(00)00322-X
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The influence of some anticholinergic drugs (atropine, benactyzine, biperiden, scopolamine) on the efficacy of antidotal treatment to eliminate soman (O-pinacolyl methylphosphonofluoridate)-induced disturbance of respiration and circulation and to protect experimental animals poisoned with supralethal dose of soman (1.5 x LD50) was investigated in a rat model with on-line monitoring of respiratory and circulatory parameters. While the oxime HI-6 in combination with atropine prevented soman-induced changes in monitored physiological parameters insuficiently and very shortly, the combination of HI-6 with benactyzine or biperiden is able to prevent soman-induced alteration of respiration and circulation much more longer. Nevertheless, only rats treated with HI-6 in combination with scopolamine were fully protected against the lethal toxic effects of soman within 2 h following soman challenge. Our findings confirm that anticholinergic drugs with the strong central antimuscarinic activity, such as benactyzine, biperiden and especially scopolamine, seem to be more effective adjuncts to HI-6 treatment of severe acute soman-induced poisoning than atropine. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:67 / 73
页数:7
相关论文
共 26 条
[1]   Antagonism of soman-induced convulsions by midazolam, diazepam and scopolamine [J].
Anderson, DR ;
Harris, LW ;
Chang, FCT ;
Baze, WB ;
Capacio, BR ;
Byers, SL ;
Lennox, WJ .
DRUG AND CHEMICAL TOXICOLOGY, 1997, 20 (03) :115-131
[2]  
BAJGAR J, 1978, ACTIV NERV SUPER, V20, P56
[3]  
Bajgar J, 1996, Acta Medica (Hradec Kralove), V39, P101
[4]   NEUROPHYSIOLOGICAL CONCOMITANTS OF SOMAN-INDUCED RESPIRATORY DEPRESSION IN AWAKE, BEHAVING GUINEA-PIGS [J].
CHANG, FCT ;
FOSTER, RE ;
BEERS, ET ;
RICKETT, DL ;
FILBERT, MG .
TOXICOLOGY AND APPLIED PHARMACOLOGY, 1990, 102 (02) :233-250
[5]   REVIEW OF OXIMES AVAILABLE FOR TREATMENT OF NERVE AGENT POISONING [J].
DAWSON, RM .
JOURNAL OF APPLIED TOXICOLOGY, 1994, 14 (05) :317-331
[6]  
ELLENWOOD EH, 1990, J PHARMACOL EXP THER, V255, P1133
[7]   DEALKYLATION AS A MECHANISM FOR AGING OF CHOLINESTERASE AFTER POISONING WITH PINACOLYL METHYLPHOSPHONOFLUORIDATE [J].
FLEISHER, JH ;
HARRIS, LW .
BIOCHEMICAL PHARMACOLOGY, 1965, 14 (05) :641-+
[8]   QUANTITATIVE INVIVO RECEPTOR-BINDING .3. TRACER KINETIC MODELING OF MUSCARINIC CHOLINERGIC RECEPTOR-BINDING [J].
FREY, KA ;
HICHWA, RD ;
EHRENKAUFER, RLE ;
AGRANOFF, BW .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1985, 82 (19) :6711-6715
[9]  
KADAR T, 1985, ARCH TOXICOL, V58, P545
[10]   Changes of acetylcholinesterase activity in various parts of brain following nontreated and treated soman poisoning in rats [J].
Kassa, J ;
Bajgar, J .
MOLECULAR AND CHEMICAL NEUROPATHOLOGY, 1998, 33 (03) :175-184