Diana G, Scotti de Carolis A, Popoli P, Pezzola A, Sagratella S
Pharmacology Department, Istituto Superiore di Sanità, Roma, Italy.
Life Sci. 1993;52(19):1547-57. doi: 10.1016/0024-3205(93)90055-8.
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.
在大鼠和小鼠中，测试了非阿片类口服镇咳药右美沙芬（DM）和卡拉美芬（CP）对N-甲基-D-天冬氨酸（NMDA）拮抗剂地佐环平（MK 801）和苯环利定（PCP）所引发的行为和脑电图效应的影响。PCP（腹腔注射1.25 - 10 mg/kg）可诱导小鼠运动/探索活动呈剂量依赖性增加/减少。DM（腹腔注射25 - 50 mg/kg）和MK 801（腹腔注射0.125 - 0.250 mg/kg）可诱导小鼠运动/探索活动增加，而CP（腹腔注射25 - 50 mg/kg）则无此作用。在小鼠旷场试验中，CP（腹腔注射12.5 mg/kg）和DM（腹腔注射12.5 mg/kg）显著增强了PCP（腹腔注射1.25 mg/kg）和MK 801（腹腔注射0.062 mg/kg）的效应。在大鼠中，PCP（腹腔注射1.25 - 10 mg/kg）可诱导出三个剂量依赖性脑电图阶段：1）皮质去同步化期增加；2）皮质背景活动振幅增加；3）皮质慢波-棘波复合体出现。尽管DM（腹腔注射高达100 mg/kg）自身仅诱导出类似PCP的脑电图第1阶段，且CP（腹腔注射高达50 mg/kg）不影响基础皮质脑电图活动，但这些药物在腹腔注射30 - 50 mg/kg剂量时，增强了PCP诱导的所有脑电图效应。这些数据支持了非阿片类镇咳药与非竞争性NMDA拮抗剂之间存在相互作用的观点。
