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Comparison of tricyclic antidepressants in rabbits: Antinociception and potentiation of the noradrenaline pressor responses

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Abstract

The antinociceptive effect on the rabbit's dental pain of 10 tricyclic antidepressants (2–5 mg/kg i.v.) was compared with their potentiation of the noradrenaline (NA) pressor responses in conscious rabbits. The receptor desensitization by tricyclic antidepressants was tested on the rabbit's isolated aortic spiral.

Tertiary amines imipramine, amitriptyline, doxepine, and trimipramine were most antinociceptive but inferior to 5 mg/kg of morphine. They were also most potent in enchancing the morphine analgesia, amitriptyline and doxepine in particular. The secondary amines desipramine and nortriptyline were less antinociceptive than their tertiary analogues imipramine and amitriptyline. The effects of opipramol and imipramine N-oxide were inconsistent. Dibenzepine and iprindole were inactive. Lithium abolished the antinociceptive action of protriptyline without modifying that of the combination of protriptyline and morphine.

The secondary amines, protriptyline and nortriptyline, proved most effective in enhancing the NA pressor response, followed by dibenzepine, desipramine, and imipramine. Opipramol, amitriptyline and iprindole were least active. Trimipramine reduced the NA pressor responses and the effect of doxepine was variable. Lithium did not modify the NA potentiation by protriptyline.

It is concluded that antinociception by tricyclic antidepressants is more likely related to their central tryptaminergic mechanisms or to local anaesthetic properties than to their adrenergic or adrenolytic activity.

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  1. Department of Pharmacology, University of Helsinki, Helsinki, Finland

    Laila Saarnivaara & M. J. Mattila

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  1. Laila Saarnivaara
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  2. M. J. Mattila
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Saarnivaara, L., Mattila, M.J. Comparison of tricyclic antidepressants in rabbits: Antinociception and potentiation of the noradrenaline pressor responses. Psychopharmacologia 35, 221–236 (1974). https://doi.org/10.1007/BF00437751

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  • DOI: https://doi.org/10.1007/BF00437751

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