IN-VIVO PHARMACOLOGICAL EFFECTS OF DIHYDRO-BETA-ERYTHROIDINE, A NICOTINIC ANTAGONIST, IN MICE

被引:60
作者
DAMAJ, MI [1 ]
WELCH, SP [1 ]
MARTIN, BR [1 ]
机构
[1] VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT PHARMACOL & TOXICOL,RICHMOND,VA 23298
关键词
NICOTINE DIHYDRO-BETA-ERYTHROIDINE; ANTINOCICEPTION; CALCIUM; MECAMYLAMINE; MICE;
D O I
10.1007/BF02245100
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The comparative in vivo pharmacology of mecamylamine and dihydro-beta-erythroidine (DH beta E) in mice was studied. Modulation of the behavioral effects (antinociception, hypomotility, motor impairment and hypothermia) of nicotine in mice by DH beta E and mecamylamine were carried out. After SC administration, DH beta E and mecamylamine were nearly equipotent in blocking nicotine's effects except for antinociception, in which mecamylamine was clearly more potent. Intrathecal injection of DH beta E was also effective in blocking the antinociceptive effect of nicotine. In vivo interaction of DH beta E with calcium and calcium channels, involved in the central actions of nicotine, showed that intrathecal administration of DH beta E failed to reduce the antinociception induced by diverse drugs which increase intracellular calcium such as thapsigargin, (+/-)-BAYK 8644 and calcium, indicating that this antagonist does not affect calcium-dependent mechanisms involved in antinociception. On the other hand, mecamylamine blocked the antinociceptive effect of the calcium modulatory drugs, suggesting that it may be acting on calcium-dependent mechanisms involved in the intracellular signaling process. We conclude that DH beta E, a nicotinic neuromuscular antagonist, is able to block some of the central actions of nicotine after systemic and intrathecal administration. The mechanism of blockade is different from that of mecamylamine, a classical ganglionic antagonist, and may involve a direct action of DH beta E on nicotine receptor.
引用
收藏
页码:67 / 73
页数:7
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