Diazoxide is a drug which was approved by FDA for the treatment of secondary hyperinsulinemia. The drug exerts its action by binding to SUR1 subunit of ATP-sensitive potassium channel that leads to the channel opening.

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.

Mecamylamine (Inversine), the first orally available antihypertensive agent, is now rarely used. Introduced as a therapeutic agent for the treatment of hypertension in the 1950s, mecamylamine was the first useful ganglionic blocking agent that was not a quarternary ammonium compound. Mecamylamine is indicated for the management of moderately severe to severe essential hypertension and in uncomplicated cases of malignant hypertension. Mecamylamine reduces blood pressure in both normotensive and hypertensive individuals. A small oral dosage often produces a smooth and predictable reduction of blood pressure. Although this antihypertensive effect is predominantly orthostatic, the supine blood pressure is also significantly reduced. Mecamylamine is a nicotinic parasympathetic ganglionic blocker. Mecamylamine administration produces several deleterious side-effects at therapeutically relevant doses. As such, mecamylamine’s use as an antihypertensive agent was phased out, except in severe hypertension. Mecamylamine easily traverses the blood-brain barrier to reach the central nervous system (CNS), where it acts as a nicotinic acetylcholine receptor (nAChR) antagonist, inhibiting all known nAChR subtypes. Since nAChRs play a major role in numerous physiological and pathological processes, it is not surprising that mecamylamine has been evaluated for its potential therapeutic effects in a wide variety of CNS disorders, including addiction.

Hydralazine is a direct-acting vasodilator that is used as an antihypertensive agent. Hydralazine works by relaxing blood vessels (arterioles more than venules) and increasing the supply of blood and oxygen to the heart while reducing its workload. It also functions as an antioxidant. It inhibits membrane-bound enzymes that form reactive oxygen species, such as superoxides. Excessive superoxide counteracts NO-induced vasodilation. Hydralazine is used for the treatment of essential hypertension, alone or as an adjunct. Also for the management of severe hypertension when the drug cannot be given orally or when blood pressure must be lowered immediately, congestive heart failure (in combination with cardiac glycosides and diuretics and/or with isosorbide dinitrate), and hypertension secondary to pre-eclampsia/eclampsia.

Pinacidil is a clinically effective vasodilator used for the treatment of hypertension.

Bethanidine is a post-ganglionic adrenergic neurone-blocking agent which exerts a marked postural hypotensive effect. The precise mechanism whereby bethanidine causes blockade of adrenergic neurones is unknown. An initial sympathomimetic effect has been demonstrated in man and animals, possibly due to release of catecholamines.

Pargyline is an irreversible selective monoamine oxidase (MAO)-B inhibitor, which possesses higher selectivity to this isoform in comparison with MAO-A. It was approved under brand name eutonyl for the treatment hypertension, but then this drug was discontinued.

Syrosingopine, a drug derived from reserpine, which was investigated for the treatment of essential hypertension. The combination of syrosingopine and a mitochondrial inhibitor for the treatment of cancer and for achieving immunosuppression was patented. This invention also relates to a fluorescence-based method for predicting syrosingopine sensitivity of a cancer cell.

Deserpidine is an ester alkaloid drug isolated from Rauwolfia canescens (family Apocynaceae) with antipsychotic and antihypertensive properties that has been used for the control of high blood pressure and for the relief of psychotic behavior. Rauwolfia alkaloids work by controlling nerve impulses along certain nerve pathways. As a result, they act on the heart and blood vessels to lower blood pressure. Deserpidine's mechanism of action is through inhibition of the ATP/Mg2+ pump responsible for the sequestering of neurotransmitters into storage vesicles located in the presynaptic neuron. The neurotransmitters that are not sequestered in the storage vesicle are readily metabolized by monoamine oxidase (MAO) causing a reduction in catecholamines.

Rescinnamine is an alkaloid isolated from Rauvolfia serpentina and approved by FDA for the treatment of hypertension. The mechanism of rescinnamine is not established, but probably resembles that of reserpine. Rescinnamine approval was discontinued by unknown reason.