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

The comparative in vivo pharmacology of mecamylamine and dihydro-beta- erythroidine (DH beta E) in mice was studied. Modulation of the behavi oral effects (antinociception, hypomotility, motor impairment and hypo thermia) of nicotine in mice by DH beta E and mecamylamine were carrie d 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 calciu m channels, involved in the central actions of nicotine, showed that i ntrathecal administration of DH beta E failed to reduce the antinocice ption induced by diverse drugs which increase intracellular calcium su ch as thapsigargin, (+/-)-BAYK 8644 and calcium, indicating that this antagonist does not affect calcium-dependent mechanisms involved in an tinociception. On the other hand, mecamylamine blocked the antinocicep tive 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 neuromuscul ar antagonist, is able to block some of the central actions of nicotin e after systemic and intrathecal administration. The mechanism of bloc kade is different from that of mecamylamine, a classical ganglionic an tagonist, and may involve a direct action of DH beta E on nicotine rec eptor.