α1-agonists bind ADRA1A,B,D

An antihypotensive agent (vasopressor agent, pressor) is any medication that tends to raise a reduced blood pressure. Antihypotensive drugs can act as vasoconstrictors to increase total peripheral resistance, others sensitise adrenoreceptors to catecholamines and the third class can increase cardiac output. Sympathomimetic drugs (also known as adrenergic drugs and adrenergic amines) are stimulant compounds which mimic the effects of endogenous agonists (the catecholamines epinephrine and norepinephrine and dopamine) of the sympathetic nervous system. Sympathomimetic drugs are used to treat cardiac arrest and low blood pressure, among other uses (Cao et al. 2003, Jensen et al. 2011, Currigan et al. 2014).<br><br>The α1-agonist drugs selectively stimulate α1-adrenoceptors, mimicking the action of epinephrine and norepinephrine signaling in the heart, smooth muscle and central nervous system (Horie et al. 1995, review Perez 2007). There are three homologous subtypes of α1-adrenoceptors: α1A, α1B, and α1D. The α1A- and α1B-adrenoceptors are expressed in the rodent and human heart (Jensen et al. 2009a), whereas the α1D-adrenoceptor is found in the coronary vasculature and mediates vasoconstriction (Jensen et al. 2009b). α1-adrenoceptors are GPCRs coupled to the heterotrimeric G protein Gq, which, upon receptor activation, activates phospholipase C (PLC). PLC cleaves phosphatidylinositol 4,5-bisphosphate (PIP2), which in turn causes an increase in inositol triphosphate (IP3) and diacylglycerol (DAG). IP3 interacts with calcium channels on the endoplasmic and sarcoplasmic reticulum, releasing Ca2+ from stores and increasing intracellular Ca2+ levels and subsequently, causes smooth muscle contraction in blood vessels, GI tract, kidney, brain, skin, bladder and the eye.<br><br>Drugs that act as α1-adrenoceptor agonists are used as vasopressors, for urinary incontinence and in nasal decongestants. Methoxamine is an brain-penetrant α1-adrenoceptor agonist (Taniguchi et al. 1999) and may be useful for stress urinary incontinence (SUI) therapy (Yoshiki et al. 2013). Oxymetazoline (SCH-9384, Vicks Sinex) is a decongestant that shrinks blood vessels in the nasal passages. Dilated blood vessels can cause nasal congestion (stuffy nose) caused by allergies or the common cold (Bende & Löth 1986). Due to its vasoconstricting properties, oxymetazoline is also used to treat nose bleeds (Krempl & Noorily 1995). Phenylephrine is a selective α1-adrenergic receptor agonist (Taniguchi et al. 1999) of the phenethylamine class used primarily as a decongestant (Johnson & Hricik 1993), as an agent to dilate the pupil, to increase blood pressure (vasopressor), and to relieve hemorrhoids. It is well tolerated at therapeutic doses, with only higher doses producing any significant rises in blood pressure (Chua & Benrimoj 1988, Gelotte & Zimmerman 2015).

抗低血压药物（血管加压剂、升压剂）是指任何有助于提升降低血压的药物。抗低血压药物可作为血管收缩剂以增加总外周阻力，另一些药物则能增强肾上腺素能受体对儿茶酚胺的敏感性，第三类药物能增加心输出量。拟交感神经药物（亦称为肾上腺素能药物和肾上腺素能胺）是一类模仿内源性激动剂（交感神经系统的儿茶酚胺肾上腺素、去甲肾上腺素和多巴胺）作用的刺激性化合物。拟交感神经药物被用于治疗心脏骤停和低血压，以及其他用途（Cao 等人，2003年，Jensen 等人，2011年，Currigan 等人，2014年）。

α1-激动剂类药物能选择性地刺激α1-肾上腺素能受体，模仿肾上腺素和去甲肾上腺素在心脏、平滑肌和中枢神经系统中的信号传导作用（Horie 等人，1995年，Perez 综述，2007年）。α1-肾上腺素能受体有三种同源亚型：α1A、α1B 和 α1D。α1A-和 α1B-肾上腺素能受体在啮齿动物和人类心脏中表达（Jensen 等人，2009a），而 α1D-肾上腺素能受体则存在于冠状动脉血管中，介导血管收缩（Jensen 等人，2009b）。α1-肾上腺素能受体是与异源三聚体G蛋白Gq偶联的G蛋白偶联受体（GPCR），在受体激活后，激活磷脂酰肌醇4，5-二磷酸（PIP2），进而导致肌醇三磷酸（IP3）和二酰甘油（DAG）的增加。IP3与内质网和肌质网上的钙通道相互作用，从储存中释放Ca2+，增加细胞内Ca2+水平，随后，导致血管、胃肠道、肾脏、大脑、皮肤、膀胱和眼睛中的平滑肌收缩。

作为α1-肾上腺素能受体激动剂的药物被用作血管加压剂、治疗尿失禁和作为鼻用去充血剂。甲氧明是一种能透过血脑屏障的α1-肾上腺素能受体激动剂（Taniguchi 等人，1999年），可能对压力性尿失禁（SUI）的治疗有益（Yoshiki 等人，2013年）。氧甲唑啉（SCH-9384，Vicks Sinex）是一种收缩鼻道血管的减充血剂。扩张的血管可以引起由过敏或普通感冒引起的鼻塞（鼻塞）（Bende 与 Löth，1986年）。由于其血管收缩特性，氧甲唑啉也被用于治疗鼻出血（Krempl 与 Noorily，1995年）。苯肾上腺素是一种选择性α1-肾上腺素能受体激动剂（Taniguchi 等人，1999年），属于苯乙胺类药物，主要用于作为减充血剂（Johnson 与 Hricik，1993年），作为散瞳剂，用于提高血压（血管加压剂）和缓解痔疮。在治疗剂量下耐受性良好，只有在高剂量下才会引起血压的显著升高（Chua 与 Benrimoj，1988年，Gelotte 与 Zimmerman，2015年）。