Non-opioid antitussives potentiate some behavioural and EEG effects of N-methyl-D-aspartate channel blockers.
The effects of the non-opioid oral antitussives dextromethorphan (DM) and caramiphen (CP) were tested against the behavioural and EEG effects elicited by the N-methyl-D-aspartate (NMDA) antagonists dizocilpine (MK 801) and phencyclidine (PCP) in rats and mice. PCP (1.25-10 mg/kg i.p.) induced a dose-dependent increase/decrease of the locomotor/exploratory activity of mice. DM (25-50 mg/kg i.p.) and MK 801 (0.125-0.250 mg/kg i.p.) induced an increase of the locomotor/exploratory activity of mice, while CP (25-50 mg/kg i.p.) did not produce such an effect. CP (12.5 mg/kg i.p.) and DM (12.5 mg/kg i.p.) significantly potentiated the effects of PCP (1.25 mg/kg i.p.) and MK 801 (0.062 mg/kg i.p.) in the open field test in mice. In rats, PCP (1.25-10 mg/kg i.p.) induced three dose-dependent EEG stages: 1) increase of the cortical desynchronization periods; 2) increase of the amplitude of cortical background activity; 3) appearance of cortical slow wave-spike complexes. Even though DM (up to 100 mg/kg i.p.) only induced PCP-like EEG stage 1 by itself, and CP (up to 50 mg/kg i.p.) did not affect basal cortical EEG activity, these drugs, at the doses of 30-50 mg/kg i.p., potentiated all the EEG effects induced by PCP. These data support the view of an interaction between non-opioid antitussives and non-competitive NMDA antagonists.
Diana
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Pharmacology Department, Istituto Superiore di Sanità, Roma, Italy.
Scotti de Carolis
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Popoli
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Pezzola
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Sagratella
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D000818:Animals; D000996:Antitussive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D003517:Cyclopentanes / Q000494:pharmacology*; D003915:Dextromethorphan / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004569:Electroencephalography / Q000187:drug effects*; D007473:Ion Channels / Q000187:drug effects*; D008297:Male; D051379:Mice; D010622:Phencyclidine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D000996:Antitussive Agents; D003517:Cyclopentanes; D007473:Ion Channels; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D003915:Dextromethorphan; C004519:caramiphen; D010622:Phencyclidine