An Analytical Reference Material
Dextrorphan (tartrate) is a phencyclidine-like metabolite of dextromethorphan, kwoun as an antitussive in cough medicines [1]. Dextrorphan (tartrate) is a noncompetitive N-methyl-d-aspartate (NMDA) antagonist that is neuroprotective in experimental models of focal brain ischemia [2]. Dextrorphan (tartrate) concentrations producing IC50 of K+-stimulated 45Ca 2+ uptake into brain synaptosomes was 200±27μM [3].
Dextrorphan (tartrate) inhibit excitatory amino acid (EAA) evoked neuronal responses 3, apparently by acting at a site on the NMDA-preferring EAA receptor or its associated Ca 2+ channel. Dextromethorphan and dextrorphan (tartrate) protect neurons from EAA-induced cytotoxicity [3].
In dextrorphan-treated patients, transient and reversible adverse effects, including nystagmus, nausea, vomiting, somnolence, hallucinations, and agitation, commonly occurred. Loading-dose escalation was stopped because of rapid-onset, reversible, symptomatic hypotension in 7 of 21 patients treated with doses of 200 to 260 mg/h. Maximum plasma levels of 750 to 1000 ng/mL were obtained in 9 patients [2].
参考文献:
[1]. Shin, E.J., Lee, P.H., Kim, H.J., et al. Neuropsychotoxicity of abused drugs: Potential of dextromethorphan and novel neuroprotective analogs of dextromethorphan with improved safety profiles in terms of abuse and neuroprotective effects. Journal of Pharmacological Sciences 106(1), 22-27 (2008).
[2]. Albers GW, Atkinson RP, Kelley RE, Rosenbaum DM; Dextrorphan Study Group. Safety, tolerability, and pharmacokinetics of the N-methyl-d-aspartate antagonist dextrorphan in patients with acute stroke.Stroke. 1995; 26:254-258.
[3]. Carpenter CL, Marks SS, Watson DL, Greenberg DA. Dextromethorphan and dextrorphan as calcium channel antagonists. Brain Res.1988; 439:372-375.
右啡烷（酒石酸盐）是右美沙芬的苯环利定样代谢物，在止咳药中用作镇咳剂 [1]。右啡烷（酒石酸盐）是一种非竞争性 N-甲基-d-天冬氨酸 (NMDA) 拮抗剂，在局灶性脑缺血的实验模型中具有神经保护作用[2]。产生 K+- 刺激 45Ca 2+ 摄入脑突触体的 IC50 的右啡烷（酒石酸盐）浓度为 200±27μM [3]。
右啡烷（酒石酸盐）抑制兴奋性氨基酸 (EAA) 诱发的神经元反应 3，显然是通过作用于偏好 NMDA 的 EAA 受体或其相关 Ca 2+ 通道上的一个位点。右美沙芬和右啡烷（酒石酸盐）保护神经元免受 EAA 诱导的细胞毒性[3]。
在接受右啡烷治疗的患者中，通常会发生短暂和可逆的不良反应，包括眼球震颤、恶心、呕吐、嗜睡、幻觉和激越。在接受 200 至 260 mg/h 剂量治疗的 21 名患者中，有 7 名因快速发作、可逆、有症状的低血压而停止负荷剂量增加。 9 名患者[2] 的最大血浆浓度为 750 至 1000 ng/mL。
| Animal experiment [2]: | |
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Animal models |
Rat |
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Preparation Method |
Slow i.v. injection of 4-6 mg/kg of dextrorphan (tartrate) |
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Dosage form |
Intravenous injection, 4-6 mg/kg |
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Applications |
I.v. injection of 4-6 mg/kg of dextrorphan (tartrate) resulted in a selective reduction of NMA-induced excitation similar to that seen during the local administration of the drug by electrophoresis. |
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参考文献: [1]: J.D. Church, D. Lodge, S.C. Berry.Differential effects of dextrorphan and levorphanol on the excitation of rat spinal neurons by amino acids.Eur J Pharmacol, 111 (1985), pp. 185-190 | |
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