α2-agonist drugs act on central α2-adrenoceptors, in the ponto-medullary region of the brain. Stimulation of central α2-adrenoceptors decreases peripheral sympathetic tone and thus a fall in blood pressure and bradycardia (van Zwieten 1980, van Zwieten et al. 1984, Noyer et al. 1994, Khan et al. 1999). Neuromodulation by α2-agonist drugs can also lead to sedation and analgesia, where they possess a good safety profile (Nguyen et al. 2017).

Clonidine and dexmedetomidine are the two major α2-agonist drugs. Clonidine is used to treat hypertension (especially in postpartum women) by stimulating α2 adrenoreceptors in the brain stem, decreasing peripheral vascular resistance and thereby lowering blood pressure (Tuimala et al. 1985, Noronh et al. 2017). Dexmedetomidine is a highly selective α2-adrenergic agonist, approved by the FDA in 1999 as a short-term (<24 hours) sedative, analgesic and anxiolytic for ICU patients (Shehabi et al. 2004, Flükiger et al. 2018, Wu et al. 2018). Apraclonidine possesses selective alpha-2 and weak alpha-1 receptor agonist activity (Cambron et al. 2011) and is used in a topical ophthalmic solution to improve blepharospasm-related eyelid closure (Wijemanne et al. 2017, Vijayakumar et al. 2017). Apraclonidine has also been used as a diagnostic test for Horner's syndrome (Kauh & Bursztyn 2015). Guanfacine is a selective α2-adrenoceptor agonist used to treat hypertension (Distler et al. 1980, Cornish 1988) and attention deficit hyperactivity disorder (ADHD) (Osland et al. 2018, Alamo et al. 2016, Stahl 2010).

Brimonidine is indicated for the lowering of intraocular pressure in patients with open-angle glaucoma or ocular hypertension (Toris et al. 1999, Gómez-Aguayo et al. 2018). As a topical gel application (Mirvaso), brimonidine is indicated for persistent facial redness of rosacea (Gold et al. 2017, Kim et al. 2017). Guanabenz is an α2-adrenoceptor agonist indicated for hypertension (Walker et al. 1982, Sorkin & Heel 1986). Tizanidine is a centrally acting α2adrenoceptor agonist used as a muscle relaxant to treat the spasms, cramping, and tightness of muscles caused by multiple sclerosis, ALS, spastic diplegia and back pain (Kamen et al. 2008, Chang et al. 2013).