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 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.
Damaj
M I
MI
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0613, USA.
Welch
S P
SP
Martin
B R
BR
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004079:Dihydro-beta-Erythroidine / Q000008:administration & dosage / Q000494:pharmacology*; D006584:Hexamethonium Compounds / Q000494:pharmacology; D066298:In Vitro Techniques; D007278:Injections, Spinal; D007700:Kinetics; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D009068:Movement / Q000187:drug effects; D009538:Nicotine / Q000378:metabolism; D018733:Nicotinic Antagonists / Q000008:administration & dosage / Q000494:pharmacology*
D000700:Analgesics; D006584:Hexamethonium Compounds; D018733:Nicotinic Antagonists; D004079:Dihydro-beta-Erythroidine; D008464:Mecamylamine; D009538:Nicotine