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In vivo pharmacological effects of dihydro-β-erythroidine, a nicotinic antagonist, in mice

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Abstract

The comparative in vivo pharmacology of mecamylamine and dihydro-β-erythroidine (DHβE) in mice was studied. Modulation of the behavioral effects (antinociception, hypomotility, motor impairment and hypothermia) of nicotine in mice by DHβE and mecamylamine were carried out. After SC administration, DHβE and mecamylamine were nearly equipotent in blocking nicotine's effects except for antinociception, in which mecamylamine was clearly more potent. Intrathecal injection of DHβE was also effective in blocking the antinociceptive effect of nicotine. In vivo interaction of DHβE with calcium and calcium channels, involved in the central actions of nicotine, showed that intrathecal administration of DHβE 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 DHβE, 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 DHβE on nicotine receptor.

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, 23298-0613, Richmond, VA, USA

    M. I. Damaj, S. P. Welch & B. R. Martin

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  1. M. I. Damaj
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  2. S. P. Welch
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  3. B. R. Martin
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Damaj, M.I., Welch, S.P. & Martin, B.R. In vivo pharmacological effects of dihydro-β-erythroidine, a nicotinic antagonist, in mice. Psychopharmacology 117, 67–73 (1995). https://doi.org/10.1007/BF02245100

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  • DOI: https://doi.org/10.1007/BF02245100

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