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).

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.

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).