Dexmedetomide (biologically active dextroisomer of medetomidine) is an alpha2-adrenergic agonist which was approved by FDA for the sedation purposes. Upon administration the drug activates the alpha2 receptors thus inhibiting the release of norepinephrine and terminating the propagation of pain signals. Also it inhibits sympathetic activity and thus can decrease blood pressure and heart rate.

Tizanidine is a short-acting drug for the management of spasticity. Tizanidine is an agonist at a2-adrenergic receptor sites and presumably reduces spasticity by increasing presynaptic inhibition of motor neurons. In animal models, tizanidine has no direct effect on skeletal muscle fibers or the neuromuscular junction, and no major effect on monosynaptic spinal reflexes. The effects of tizanidine are greatest on polysynaptic pathways. The overall effect of these actions is thought to reduce facilitation of spinal motor neurons. Side effects include dizziness, drowsiness, weakness, nervousness, hallucinations, depression, vomiting, dry mouth, constipation, diarrhea, stomach pain, heartburn, increased muscle spasms, back pain, rash, sweating, and a tingling sensation in the arms, legs, hands, and feet.

Clonidine is a centrally acting α2 adrenergic agonist and imidazoline receptor agonist used to treat high blood pressure, attention deficit hyperactivity disorder, anxiety disorders, tic disorders, withdrawal (from either alcohol, opioids, or smoking), migraine, menopausal flushing, diarrhea, and certain pain conditions. Clonidine treats high blood pressure by stimulating α2 receptors in the brain, which decreases peripheral vascular resistance, lowering blood pressure. It has specificity towards the presynaptic α2 receptors in the vasomotor center in the brainstem. This binding decreases presynaptic calcium levels, thus inhibiting the release of norepinephrine (NE). It has also been proposed that the antihypertensive effect of clonidine is due to agonism on the I1 receptor (imidazoline receptor), which mediates the sympatho-inhibitory actions of imidazolines to lower blood pressure. Clonidines mechanism of action in the treatment of ADHD is to increase noradrenergic tone in the prefrontal cortex (PFC) directly by binding to postsynaptic α2A adrenergic receptors and indirectly by increasing norepinephrine input from the locus coeruleus. Clonidine indicated in the treatment of hypertension. Clonidine hydrochloride tablets may be employed alone or concomitantly with other antihypertensive agents. The US Food and Drug Administration (FDA) has approved clonidine for the treatment of attention deficit hyperactivity disorder (ADHD), under the trade name of Kapvay alone or with stimulants in 2010, for pediatric patients aged 6–17 years.

Methyldopate hydrochloride [levo-3-(3,4-dihydroxyphenyl)-2-methylalanine, ethyl ester hydrochloride] is the ethyl ester of methyldopa, supplied as the hydrochloride salt with a molecular weight of 275.73. Methyldopate hydrochloride is more soluble and stable in solution than methyldopa and is the preferred form for intravenous use. Methyldopate hydrochloride is an alpha adrenergic agonist that has both central and peripheral nervous system effects. Its primary clinical use is as an antihypertensive agent.

Guanabenz, an antihypertensive agent for oral administration-, is an aminoguanidine derivative, 2,'6-dichlorobenzylideneamina-guanidine acetate. It is white to an almost white powder having not more than a slight odor. Sparingly soluble in water and in 0.1 N hydrochloric acid; soluble in alcohol and in propylene glycol. Guanabenz is an orally active central alpha-2 adrenergic agonist. Its antihypertensive action appears to be mediated via stimulation of central alpha-adrenergic receptors, resulting in a decrease of sympathetic outflow from the brain at the bulbar level to the peripheral circulatory system. In clinical trials, guanabenz acetate, given orally to hypertensive patients, effectively controlled blood pressure without any significant effect on glomerular filtration rate, renal blood flow, body fluid volume or body weight. The Myelin Repair Foundation and the National Institutes of Health (National Institute of Neurological Disorders and Stroke) are developing guanabenz for the treatment of multiple sclerosis. Unlike the currently available treatment for multiple sclerosis that suppresses the immune system, guanabenz, an FDA approved the drug for the treatment of high blood pressure, has a potential to reduce the loss of myelin by protecting and repairing myelin-producing cells in the brain from damage. Phase I development is underway in the US.

Etiguanfacine, also known as SSP-1871, is an α2-adrenoreceptor agonist.

Methyldopate hydrochloride [levo-3-(3,4-dihydroxyphenyl)-2-methylalanine, ethyl ester hydrochloride] is the ethyl ester of methyldopa, supplied as the hydrochloride salt with a molecular weight of 275.73. Methyldopate hydrochloride is more soluble and stable in solution than methyldopa and is the preferred form for intravenous use. Methyldopate hydrochloride is an alpha adrenergic agonist that has both central and peripheral nervous system effects. Its primary clinical use is as an antihypertensive agent.