Effects of L-tryptophan on the development of tolerance to the antitussive effects of dihydrocodeine.

Kamei, Junzo; Mori, Tomohisa; Kasuya, Yutaka

doi:10.1254/jjp.55.403

Cited by 1 publication

(1 citation statement)

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“…The serotonin precursor L-tryptophan potentiated the antitussive action of dihydrocodeine (Kamei et al 1990) and the serotonin antagonist methysergide reduced the antitussive effects of dextromethorphan and dihydrocodeine in rats (Kamei et al 1986a, 1996). L-Tryptophan treatment also prevented the development of tolerance in rats to the antitussive effects of dihydrocodeine (Kamei et al 1991b). Morphine dependence elicits a reduced sensitivity to opioid and non-opioid antitussives and these effects were associated with a reduction on serotonin receptors in the brainstems of morphine-dependent rats (Kamei et al 1989).…”

Section: Receptor Specificitymentioning

confidence: 99%

Central Mechanisms II: Pharmacology of Brainstem Pathways

Bolser

2009

Pharmacology and Therapeutics of Cough

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Following systemic administration, centrally acting antitussive drugs are generally assumed to act in the brainstem to inhibit cough. However, recent work in humans has raised the possibility of suprapontine sites of action for cough suppressants. For drugs that may act in the brainstem, the specific locations, types of neurones affected, and receptor specificities of the compounds represent important issues regarding their cough-suppressant actions. Two medullary areas that have received the most attention regarding the actions of antitussive drugs are the nucleus of the tractus solitarius (NTS) and the caudal ventrolateral respiratory column. Studies that have implicated these two medullary areas have employed both microinjection and in vitro recording methods to control the location of action of the antitussive drugs. Other brainstem regions contain neurones that participate in the production of cough and could represent potential sites of action of antitussive drugs. These regions include the raphe nuclei, pontine nuclei, and rostral ventrolateral medulla. Specific receptor subtypes have been associated with the suppression of cough at central sites, including 5-HT1A, opioid (μ, κ, and δ), GABA-B, tachykinin neurokinin-1 (NK-1) and neurokinin-2, non-opioid (NOP-1), cannabinoid, dopaminergic, and sigma receptors. Aside from tachykinin NK-1 receptors in the NTS, relatively little is known regarding the receptor specificity of putative antitussive drugs in particular brainstem regions. Our understanding of the mechanisms of action of antitussive drugs would be significantly advanced by further work in this area.

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