Idazoxan hydrochloride (RX 781094 hydrochloride, IDA) is a ligand for α2-adrenergic and imidazoline receptors with a molecular weight of 241. It binds to mitochondrial membranes and promotes apoptosis in pancreatic β cells[1]. Additionally, it competitively antagonizes the central hypotensive effects of imidazoline-like active molecules (IMs) [2]. It's worth noting that Idazoxan hydrochloride has been reported to improve motor symptoms in Parkinson's disease, levodopa-induced motor disturbances, and experimental Parkinson's syndrome.
In vitro studies demonstrate that incubating rat glioma C6 cells with 10 μM Idazoxan hydrochloride for 5 days leads to a 23% reduction in β-adrenergic receptor numbers and a 37% decrease in isoproterenol-induced cAMP accumulation[5]. Furthermore, Idazoxan hydrochloride exhibits cytotoxicity at concentrations of 0.05-1.0 mg/ml against mouse lung cancer cells (3LL) and human prostate cancer cells (DU-145), as well as other cancer cell lines including breast, gastric, ovarian, and non-Hodgkin's lymphoma[1].
Idazoxan hydrochloride has shown efficacy in reversing fluphenazine-induced catalepsy in male CD-COBS rats when subcutaneously injected at doses ranging from 0.16 to 5 mg/kg for a duration of 1 hour, with an ED50 of 0.25 mg/kg[3]. Intrathecal injection of Idazoxan hydrochloride (30 µg/10 µL) in SNL6W rats can enhance the endogenous analgesic index NSIA following 7,8-DHF treatment[4].
[1]. GF Eilon, L Weisenthal, M Stupecky,et al. Antineoplastic activity of idazoxan hydrochloride.[J]. Cancer Chemotherapy and Pharmacology,2009(64),1157-1163.
[2]. Bousquet P, et al. Participation of imidazoline receptors and alpha(2-)-adrenoceptors in the central hypotensive effects of imidazoline-like drugs. Ann N Y Acad Sci. 1999 Jun 21;881:272-8.
[3]. Roberto W Invernizzi, et al. The α2-Adrenoceptor Antagonist Idazoxan Reverses Catalepsy Induced by Haloperidol in Rats Independent of Striatal Dopamine Release: Role of Serotonergic Mechanisms. Neuropsychopharmacology volume 28, 2003: 872-879.
[4]. Kato D , Suto T , Obata H ,et al. Spinal Activation of Tropomyosin Receptor Kinase-B Recovers the Impaired Endogenous Analgesia in Neuropathic Pain Rats.[J].Anesth Analg, 2019(2).
[5]. Manji H K , Chen G , Bitran J A ,et al. Idazoxan down-regulates beta-adrenoceptors on C6 glioma cells in vitro.[J].European Journal of Pharmacology Molecular Pharmacology, 1992, 227(3):275-282.
盐酸咪唑克生（Idazoxan hydrochloride ，RX 781094 hydrochloride ，IDA）是一种分子量为241的α2-肾上腺和咪唑啉受体配体[1]。它与线粒体膜结合并促进胰腺β细胞的凋亡, 还可竞争性地拮抗唑啉样活性分子 (IMs) 的中枢性降压作用[2]。盐酸咪唑克生还可改善帕金森病、左旋多巴诱导的运动障碍和实验性帕金森综合征的运动症状。
在体外，用10 μM盐酸咪唑克生孵育大鼠神经胶质瘤C6细胞5天，可使β-肾上腺素受体数目减少23%，异丙肾上腺素诱导的cAMP蓄积减少37%[5]。此外，盐酸咪唑克生在0.05-1.0 mg/ml的浓度下对鼠肺癌细胞3LL和人前列腺癌细胞DU-1453都具有细胞毒性，且对乳腺癌、胃癌、肺癌、卵巢癌和前列腺癌以及非霍奇金淋巴瘤的等分试样也具有细胞毒性[1] 。
在体内，雄性CD-COBS大鼠皮下注射盐酸咪唑克生0.16-5 mg/kg，持续1小时治疗，可以有效逆转氟哌啶醇诱导的僵住症，ED50为0.25 mg/kg[3]。SNL6W大鼠鞘内注射盐酸咪唑克生（30 µ g/10 µL）可以提高7,8-DHF 治疗的内源性镇痛指标NSIA[4]。