DL-Tetrahydropalmatine (dl-THP), an active component isolated from Corydalis species (a Chinese herbal medicine). dl-THP has inhibitory effects on liver injury induced by carbon tetrachloride in mice. The drug demonstrated anxiolytic and anti-nociceptive effects in animal models. dl-THP may act through inhibition of amygdaloid dopamine release to inhibit an epileptic attack – it is a very effective anti-epileptogenic and anticonvulsant agent. dl-THP has been found to have antihypertensive effects. It acts through the 5-HT2 and/or D2-receptor antagonism in the hypothalamus to induce hypotension and bradycardia in rats.

Isosorbide 2-mononitrate is a pharmacologically active metabolite of isosorbide dinitrate, an organic nitrate isosorbide dinitrate indicated for the prevention of angina pectoris due to coronary artery disease. It activates guanylate cyclase.

4-Hydroxychalcone is found in herbs and spices. 4-Hydroxychalcone is a constituent of Glycyrrhiza glabra (licorice) roots. 4-hydroxychalcone is a 17beta-hydroxysteroid dehydrogenase inhibitor. 4-hydroxychalcone inhibits TNFα-induced NF-κB activation via proteasome inhibition. Treatment with 40 mg/kg 4HCH reduced systolic hypertension, serum IL-1β, and TNF-α levels and suppressed the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and renal injury. The impact of 4-Hydroxychalcone on the hyperaldosteronism, inflammation, and kidney injury provides new insights for the future development of therapeutic strategies in resistant hypertension.

Eupatorin is a natural flavonoid isolated from the herbs of Eupatorium semiserratum. It has the anti-inflammatory and anti-proliferative properties, which may be utilized in the development of novel anti-inflammatory and anti-tumor treatments. Eupatorin moderately inhibited human cytochrome P450 1A2 (CYP1A2). Eupatorin showed IC50 values of 0.4 ug/mL on T. cruzi epimastigotes and 61.8 ug/mL on trypomastigotes, respectively. It was demonstrated, that eupatorin exerts a vasorelaxative effect on aortic rings through the NO/sGC/cGMP and PGI2 pathways, calcium and potassium channels, muscarinic and beta-adrenergic receptors.

Syringic acid (SYRA) is a potential antioxidant used in traditional Chinese medicine and is an emerging nutraceutical. Current reports claim its potential anti-angiogenic, anti-glycating, anti-hyperglycaemic, neuroprotective, and memory-enhancing properties in various animal models. Syringic acid (SA) possesses anti-obesity, anti-inflammatory and anti-steatotic effects via the regulation of lipid metabolic and inflammatory genes. SA is likely to be a new natural therapeutic agent for obesity or non-alcoholic liver disease. Syringic acid reduces oxidative stress and axonal degeneration in rat sciatic nerve after ischemia/reperfusion injury. Syringic acid may play a role in the treatment of peripheral nerve injuries due to ischemia/reperfusion.

5-carboxamidotryptamine (5-CT) is a 5-HT1 agonist with high affinity at 5-HT1A, 5-HT1B, 5-HT1D, 5-HT5 and 5-HT7 receptors. As one of the first compounds reported active at 5-HT1B, 5-carboxamidotryptamine was originally investigated as a potential treatment for migraine. During preclinical studies, 5-CT was found to cause vasodilatation of carotid circulation and hypotension in animals, effects that were later attributed to potent agonist activity at 5-HT7. Subsequent structural modifications of 5-CT led to the discovery of the anti-migraine drug sumatriptan. 5-CT is primarily used as a pharmacological tool for study of 5-HT1 and 5-HT7 mediated functional responses.

Staurosporine is an alkaloid isolated from the culture broth of Streptomyces staurosporesa. It exerts antimicrobial, hypotensive, and cytotoxic activity. The main biological activity of staurosporine is the inhibition of protein kinases through the prevention of ATP binding to the kinase. This is achieved through the stronger affinity of staurosporine to the ATP-binding site on the kinase. Staurosporine is a prototypical ATP-competitive kinase inhibitor in that it binds to many kinases with high affinity, though with little selectivity. It is a potent, cell permeable protein kinase C inhibitor with an IC50 of 0.7 nM. At higher concentration (1-20 nM), staurosporine also inhibits other kinases such as PKA, PKG, CAMKII and Myosin light chain kinase (MLCK). At 50-100 nM, it is a functional neurotrophin agonist, promoting neurite outgrowth in neuroblastoma, pheochromocytoma and brain primary neuronal cultures. At 0.2- 1 uM, staurosporine induces cell apoptosis. Staurosporine is also a potent GSK-3β inhibitor with a reported IC50 value of 15 nM. In research, staurosporine is used to induce apoptosis. It has been found that one way in which staurosporine induces apoptosis is by activating caspase-3. Staurosporine was discovered to have biological activities ranging from anti-fungal to anti-hypertensive. The interest in these activities resulted in a large investigative effort in chemistry and biology and the discovery of the potential for anti-cancer treatment. Staurosporine induces apoptosis by multiple pathways and that the inhibition of more than one kinase is responsible for its potent activity. Because the mechanism of action of staurosporine is distinct from traditional anticancer drugs, this may warrant further preclinical evaluations of the antitumor potential of new staurosporine derivatives either alone or in combination with death ligands or conventional chemotherapeutic drugs.

1-Phenyl-3-pyrazolidinone (phenidone) is a dual inhibitor of cyclooxygenase (COX) and lipoxygenase (LOX). Phenidone inhibits both the LO (lipoxygenase) and Cox (cyclooxygenase) pathways, the synthesis of Fos-related antigen protein, and is described as an anti-inflammatory and anti-oxidant compound. Phenidone is a potent hypotensive agent in the spontaneously hypertensive rat. Phenidone was also the best in suppressing LPS induced neurotoxicity, where the more potent neuroprotection by phenidone may be attributable to the synergistic effects of dual COX and LOX inhibition. Therefore, dual inhibitors of COX and LOX, such as phenidone, represent valuable candidates for the development of novel drugs for inflammation-related neurodegenerative disorders including PD.

CGS -21680 is an adenosine A2 receptor agonist with IC50 of 22 nM, exhibits 140-fold over A1 receptor. In an isolated perfused working rat heart model, CGS -21680 effectively increases coronary flow with an ED25 value of 1.8 nM. CGS-21680 binds adenosine A2 receptor with high affinity (Kd = 15.5 nM). Novartis originated CGS- 21680 in Switzerland and discontinued its development later.

Y-26763 is an active metabolite of Y-27152. Y-26763 is the novel K channel opener. It has been found to activate K channels in both cardiac myocytes and in smooth muscle cells from various tissues, suggesting that the compound has a non-specific effect on SUR1 and SUR2 channel subunits. Y-26763 well tolerated in healthy volunteers, and its pharmacologic effects were likely caused by vasodilation, which could make it an effective antihypertensive agent. At doses of 0.5 mg or higher, participants experienced headaches and palpitations, which were probably due to the vasodilatory effects and did not require treatment. Y-26763 partially protected against glycerol-induced acute renal failure. Also, it reduces infarct volume in focal cerebral ischemia in rats.