5-Nitro-2-(3-phenylpropylamino)benzoic Acid (NPPB) is a potent Cl- channel blocker, identified through an optimization study of the diphenylamine-2-carboxylate core which demonstrates the basic Cl- channel blocking activity. NPPB also demonstrates suppression of prostaglandin E2 release with an IC50 of 8 μM, presumed to be a Cox (cyclooxygenase) inhibitor given its structural similarity to fenamic acid-type Cox inhibitors. It is also a GPR35 agonist. NPPB activates the GPR35-Gi/o and GPR35-G16 pathways in human embryonic kidney 293 (HEK293) cells and induces intracellular calcium mobilization in a concentration-dependent manner in HEK293 cells coexpressing human, rat or mouse GPR35 and the chimeric G protein G(qi5).

Panaxatriol is a triterpene sapogenin originally found in species of Panax (ginseng) that exhibits anti-inflammatory, hepatoprotective, anti-arrhythmic, and antioxidative activities. Panaxatriol increases expression of heme oxygenase 1 (HO-1) and activation of Nrf2 signaling in neurons in a PI3K/Akt-dependent manner. Panaxatriol also decreases acetaminophen-induced increases in ALT and TNF-α, preventing liver injury in vivo. Additionally, panaxatriol inhibits Ca2+ channels, decreasing channel open time and open state probability in vitro and displaying anti-arrhythmic potential. Panaxatriol is a tyrosine hydroxylase inducer. It shows neuroprotective and cardioprotective effects in vivo. Panaxatriol enhances antioxidant activity and inhibits mitochondria-mediated apoptosis. Pretreatment with ginseng total saponin, especially panaxatriol, ameliorates I/R-induced myocardial damage and this protection is caused by reducing oxidative stress. Panaxatriol can relieve myelosuppression induced by radiation injury. The abilities of regulating the expression of hemopoietic growth factor GM-CSF and promoting the maturation of bone marrow cells may be responsible for some of these beneficial effects.

Paxilline is a toxic, tremorgenic indole alkaloid produced by Penicillium paxilli. Paxilline is inhibitor of BK channels, and is widely used as a tool compound to test role of BK channels in various conditions. Paxilline demonstrated therapeutic benefit in preclinical model of acute pancreatitis, and was able to induce apoptosis of glioma cell lines in vitro.

p-Chlorobenzoic acid is a major metabolite of analgesic agent zomepirac sodium in rat (present as conjugates) and mouse and a minor one in monkey and man. It is a metabolite of antidepressant Lofepramine hydrochloride, and anxiolytic and a muscle relaxant Chlormezanone too. Sodium salt of p-Chlorobenzoic acid is used as a preservative. p-Chlorobenzoic acid may prove useful clinically to prevent and reverse the accumulation of toxic levels of acyl- and arylCoA esters. If the hepatic damage in Reye’s Syndrome is due to the dead-end formation of the CoA esters of acyl- and aryl-CoA esters, then p-chlorobenzoic acid may block their formation, thereby relieving the inhibitions of gluconeogenesis and urea synthesis and preventing some of the damage to the liver.

Estragole (ES) is a natural constituent of a number of plants (e.g. tarragon, sweet basil and sweet fennel) and their essential oils have been widely used in foodstuffs as flavouring agents. Estragole ES was given GRAS Generally Recognized As Safe status by the Flavor and Extract Manufacturer’s Association FEMA, 1965 and is approved by the Food and Drug Administration for food use 21 CFR code of Federal Regulation 121.1164 . Several studies with oral, i.p. or s.c. administration to CD-1 and B6C3F1 mice have shown the carcinogenicity of ES. In vivo and in vitro experimental assays have shown that EST has sedative, anticonvulsant, antioxidant, antimicrobial, and anesthetic activity.

HMR 1556 is a blocker of the slow component of the delayed rectifier potassium current (IKs). It is being preclinically developed by sanofi-aventis in Germany as an oral agent for the treatment of atrial fibrillation.

Pircotoxinin is a component of pircotoxin, a poisonous compound from Anamirta cocculus. It exerts its action by blockade of anion channels, such as GABA-A or GlyR.