Effects of Methysergide on the Cough Reflex

Abstract

Abstract-The present study had two basic purposes: 1) to observe the effect of methysergide on the cough reflex and 2) to investigate the effect of methysergide on the antitussive effect of dextromethorphan.Male and female cats were anes thetized with pentobarbital-Na.Respiration and cough reflex were measured using a pneumotachograph via a cannula inserted into the trachea. The cough reflex was elicited by electrical stimuli to the superior laryngeal nerve. Methyser gide (3 mg) injected into the vertebral artery increased the number of coughs and respiratory frequency.Dextromethorphan in a dose of 3 mg inhibited the cough reflex. Methysergide (1 and 3 mg) reduced the antitussive effect of dextrome thorphan in a dose-dependent manner, but did not inhibit the excitatory effect on respiratory frequency.These findings might indicate that the central serotonergic system has an inhibitory role on the cough reflex and may be related to the anti tussive mechanisms of dextromethorphan.

Antitussive effects of GABAB agonists in the cat and guinea‐pig

“…Other agents known to have antitussive effects in animal models include dopamine receptor agonists (Kamei et al, 1987a), N-methyl-D-aspartate antagonists (Kamei et al, 1989) and the peripherally acting opioid agonist BW 443C (Adcock et al, 1988). Furthermore, the use of 5-hydroxytryptamine (5-HT) receptor antagonists and depletion of brain (5-HT) levels have suggested an inhibitory effect of this monoamine on cough (Kamei et al, 1986;Kamei et al, 1987b).…”

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

“…The mechanism of development of tolerance to the antitussive effects of dihydro codeine is not well known. A considerable body of evidence supports the involvement of brain serotonin receptors in the antitussive ac tion of opioid drugs (2,5,6). Previously, we demonstrated that rats treated chronically with morphine develop tolerance to the antitussive effects of morphine and dihydrocodeine (2).…”

Central Mechanisms II: Pharmacology of Brainstem Pathways

“…For example, in the rat depletion of serotonin attenuated the antitussive effect of morphine, dihydrocodeine, and dextromethorphan (Kamei et al 1987b). 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). In cats, the serotonin precursor 5-hydroxytryptophan inhibited cough (Kamei et al 1986b) and methysergide increased cough number and reduced the antitussive effects of dextromethorphan (Kamei et al 1986a). In humans, serotonin and 5-hydroxytryptamine both inhibited cough due to inhalation of low-chloride solutions, but not coughing elicited by capsaicin aerosols (Stone et al 1993).…”