Glyceryl 2-nitrate (G-2-N) is the major metabolite of glyceryl trinitrate. Strips of rat aorta contracted with potassium chloride or with norepinephrine were relaxed by G-2-N. After oral administration to the anaesthetized rat or to the conscious dog G-2-N exhibited antianginal and hypotensive activity. The hypotensive and also cardiovascular activity of G-2-N lasted much longer than that of glyceryl trinitrate.

Glyceryl 1-nitrate (G-1-N) is an intermediate metabolic product in the stepwise de-esterification of glyceryl trinitrate (GTN) in animals and humans. It belongs to the group of orally effective longacting antianginal nitrates. In anesthetized rabbits, intravenous (L) G-1-N reduced the blood pressure slightly more than (D) G-1-N, while in the conscious dog the blood pressure lowering effect of (D) G-1-N was greater and had a much longer duration (4-6 versus 2 h) than that of (L)G-1-N. The differences in dogs are probably explained by enantiospecific pharmacokinetics: (D) G-1-N had higher plasma levels and showed a longer half-life of elimination than (L) G-1-N. From the pharmacokinetic point of view, the drug offers clear advantage over glyceryl trinitrate in clinical use: G-1-N is orally available - owing to its relatively low clearance it stays much longer in the body than GTN - kinetic parameters are predictable with low coefficients of variation - and the denitration products of G-1-N are expected to be pharmacologically neutral.

Delsoline is a Nicotinic receptor antagonist, ganglion blocker; exhibits weak affinity at brain α-bungarotoxin-sensitive nicotinic acetylcholine receptors.

Benzamil is a derivative of amiloride, a potassium sparing diuretic, and is an inhibitor of Na+/H+ and Na+/Ca++ channels. Amiloride works by directly blocking the epithelial sodium channel (ENaC) thereby inhibiting sodium reabsorption in the distal convoluted tubules and collecting ducts in the kidneys (this mechanism is the same for triamterene). This promotes the loss of sodium and water from the body, but without depleting potassium. Benzamil has being shown to attenuate the development of hypertension in Dahl salt-sensitive rats. Benzamil has been studied as a possible treatment for cystic fibrosis. Benzamil was suggested to be a useful sodium channel blocker for the long-term treatment of the biochemical defect in the lungs of patients with cystic fibrosis.

Epipinoresinol is an important component of the medicinal herb Eucommia ulmoides, which has a substantial reputation as an effective antihypertensive remedy. Epipinoresinol (EPR) belongs to the group of furofuran-type lignans consisting of two phenylpropane units. (+)-epipinoresinol exhibited antiplatelet aggregation activity. It also exhibited inhibitory effects on nitric oxide production. Epipinoresinol possess antiproliferative activity.

BAY-41-2272 is a direct and NO-independent soluble guanylate cyclase (sGC) stimulator. It sensitizes sGC to nitric oxide (NO), its physiological stimulator, and contains antiplatelet activity. BAY-41-2272 is an inhibitor of GCS. BAY-41-2272 inhibits platelet aggregation (IC50 = 36 nM) and phenylephrine-induced contractions of rabbit aorta (IC50 = 0.30 uM). BAY-41-2272 also reduces vascular smooth muscle growth through cAMP- and cGMP-dependent PKA and PKG pathways. BAY-41-2272 not only sensitized NO-sensitive GC toward activation by NO but also, with comparable potency, inhibited cGMP degradation by PDE5. BAY-41-2272 may provide a novel therapeutic compound for treating chronic hypoxic pulmonary hypertension.

C-curarine-III chloride (Methvin) is a short-acting selective sympathetic ganglioblocker with weak antagonist activity on the nicotinic receptor at the neuromuscular junction; hypotensive. In test animals the drug produces a well-marked and short-term (easily controllable) hypotensive effect, without causing any histamine-like and direct vasodilation action. When used in relatively high doses methvin blocks the neuro-muscular conduction, potentiates the action of major muscle relaxants. A study of methvin in clinical conditions confirmed its high gangliolytic activity previously revealed in experiments.

Veratridine (VTD), an alkaloid derived from the Liliaceae plant shows anti-tumor effects. Veratridine is also an agent that opens voltage dependent Na+ channels, blocks Na+ channel activation, and induces Ca2+ influx. The compound has been observed to be an alkaloid neurotoxin used to amplify sodium permeability. Studies report that Veratridine can trigger exocytosis and induce Ca2+ oscillations. Furthermore, Veratridine has been shown to effect the mitochondrial respiratory chain complexes, induce release of noradrenaline, and increase superoxide anion production. Veratridine competes with BTX binding in a mutually exclusive manner. However, the pharmacological effects of veratridine on Na+ channels are quite different from those of BTX. First, veratridine reduces the single Na+ channel conductance drastically whereas BTX does not. Veratridine therefore is regarded as a partial agonist and BTX as a full agonist of Na+ channels. Second, under voltage clamp conditions BTX binds practically irreversibly to Na+ channels whereas veratridine readily dissociates from its binding site. Both of these drugs, however, bind preferentially to the open state of Na+ channels. The BTX resistant Na+ channels in Phyllobates frogs remain sensitive to veratridine. The ceveratrum alkaloids, including Veratridine, have a characteristic hypotensive effect not directly involving the CNS. They slow the heart and lower arterial blood pressure by reflexly stimulating medullary vasomotor centers without decreasing cardiac output (Bezold–Jarisch effect). These agents were introduced in the 1950s as antihypertensive agents; however, they were found to have a narrow therapeutic index and their use was discontinued.

8-Hyroxy-2-Dipropylaminotetralin Hydrobromide (8-OH-DPAT) is a chemical predominantly used in research settings. It is widely regarded as the first identified complete agonist of the 5-HT1a receptor, for which it has a Ki = 3.18 nM. 8-OH-DPAT also acts as an agonist of the 5-HT7 receptor, and as a substrate of the Sodium dependent serotonin transporter (SERT). Although it has never progressed to human clinical trials 8-OH-DPAT has been studied in animal models for a number of conditions both for its own potential and as a benchmark for other compounds.

ML-9 is a selective inhibitor of MYLK and CaMK that acts by delaying MYLK phosphorylation through binding at or near the ATP binding site. This naphthalenesulfonamide derivative has been shown to inhibit insulin-stimulated 2-deoxyglucose transport (IC50 = 27 μM), PP-1 activation in adipocytes, PKA, Akt1 (PKB) and Rsk (S6 kinase). ML-9 was also observed to disrupt microfilament bundles with accompanying decrease in P32 incorporation in rat astrocytes. Carbachol illicited cationic currents were inhibitied with ML-9 (IC50 = 7.8 uM) in HEK293 cells. ML-9 has also demonstrated to inhibit natural killer cell lytic acitivity by regulating microfilament contraction as well as catecholamine secretion in intact and permeabilized chromaffin cells. In addition, agonist-induced Ca2+ entry into endothelial cells was completely abolished in the presence of ML-9. ML-9 was found to be a new type of vascular relaxant. ML-9 produced the relaxation of vascular strips contracted by high K+. The relaxation induced by this compound was not affected by treatment with adrenergic and cholinergic blocking agents. Thus, the ML-9-induced relaxation is not due to a block of membrane receptor-associated mechanisms; rather it has an effect on more basic and common events in smooth muscle contraction. Moreover, ML-9 inhibited the Ca2+-induced contraction in chemically skinned vascular smooth muscle cells, suggesting that ML-9 is not a “calcium channel blocker.”