Influence of nimodipine and diltiazem, alone and in combination, on phencyclidine-induced effects in rats: an EEG and behavioural study.
The influence of nimodipine and/or diltiazem on the EEG and behavioural effects induced by phencyclidine (PCP) was assessed in adult male Wistar rats. Nimodipine (2 and 10 mg/kg i.p.) and diltiazem (25-100 mg/kg i.p.) significantly potentiated both EEG (increase in background activity voltage, incidence of clustered slow waves) and behavioural (ataxia mean intensity) effects of PCP (5 mg/kg i.p.). A synergistic effect between low, ineffective doses of both nimodipine (0.5 mg/kg i.p.) and diltiazem (5 and 10 mg/kg i.p.) was also found. These data confirm the recent finding of a positive allosteric modulation existing between benzothiazepine (diltiazem) and dihydropyridine (nimodipine) binding sites. They also suggest that the modulation of calcium channels may play a pivotal role in the expression of PCP-induced effects.
Popoli
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P
Pharmacology Department, Istituto Superiore di Sanità, Roma, Italy.
Benedetti
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M
Scotti de Carolis
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A
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004110:Diltiazem / Q000494:pharmacology*; D004357:Drug Synergism; D004569:Electroencephalography / Q000187:drug effects*; D008297:Male; D009553:Nimodipine / Q000494:pharmacology*; D010622:Phencyclidine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D009553:Nimodipine; D004110:Diltiazem; D010622:Phencyclidine