Nickel(II) chloride (NiCl2), a water soluble salt of Nickel, is a toxic and carcinogenic environmental and occupational pollutant, which has been shown to be carcinogenic to the lungs and nasal passages, in cases of long-term inhalation exposure. It was approved that NiCl2 was a potential genotoxicity caused indirect DNA damage by the production of ROS. In addition was conducted studies to evaluate the precise mechanism of Ni toxicology. And it was shown, thet NiCl2 induced and caused cell cycle G2/M phase arrest via p53-dependent pathway and generated inflammatory response by NF-κB pathway activation.

Levobupivacaine (CHIROCAINE®) is a (S)-enantiomer of bupivacaine and it is related chemically and pharmacologically to the amino amide class of local anesthetics. Local anesthetics block the generation and the conduction of nerve impulses by increasing the threshold for electrical excitation in the nerve, by slowing propagation of the nerve impulse, and by reducing the rate of rise of the action potential. In general, the progression of anesthesia is related to the diameter, myelination, and conduction velocity of affected nerve fibers. Clinically, the order of loss of nerve function is as follows: 1) pain, 2) temperature, 3) touch, 4) proprioception and 5) skeletal muscle tone. Levobupivacaine (CHIROCAINE®) is a safer alternative for regional anesthesia than bupivacaine. It demonstrated less affinity and strength of depressant effects onto myocardial and central nervous vital centers in pharmacodynamic studies, and a superior pharmacokinetic profile.

Mibefradil is a calcium channel blocker, chemically unlike other compounds in the class, that was approved by the Food and Drug Administration (FDA), U.S.A. in June 1997 for the treatment of patients with hypertension and chronic stable angina. Shortly following its introduction, mibefradil was withdrawn from the market in the U.S.A. as well as in Europe. The reason for the voluntary withdrawal of the drug by Roche laboratories was claimed to be the result of new information about potentially harmful interactions with other drugs. Mibefradil is calcium channel blocker with moderate selectivity for T-type Ca2+ channels displaying IC50 values of 2.7 uM and 18.6 uM for T-type and L-type channels respectively. Mibefradil is a tetralol calcium channel blocking agent that inhibits the influx of calcium ions across both the T (low-voltage) and L (high-voltage) calcium channels of cardiac and vascular smooth muscle, with a greater selectivity for T channels. Vasodilation occurs in vascular smooth muscle, causing a decrease in peripheral vascular resistance and a resulting decrease in blood pressure. Mibefradil causes a slight increase in cardiac output during chronic dosing. Mibefradil slows sinus and atrioventricular (AV) node conduction, producing a slight reduction in heart rate and a slight increase in the PR interval. It has also been shown to slightly lengthen the corrected sinus node recovery time and AH interval and to raise the Wenckebach point. The mechanism by which mibefradil reduces angina is not known, but is thought to be attributed to a reduction in heart rate, total peripheral resistance (afterload), and the heart rate-systolic blood pressure product at any given level of exercise. The result of these effects is a decrease in cardiac workload and myocardial oxygen demand. Mibefradil has been repurposed from an abandoned antihypertensive to a targeted solid tumor treatment, and it has been rescued from drug-drug interactions by using short-term dose exposure. Tau is using the early success of mibefradil as a proof of concept to build a platform technology of Cav3 blockers for broad antitumor applications in combination with new targeted cancer therapies, well-established.

Moricizine is an antiarrhythmic agent previously marketed as Ethmozine. It was used for prophylaxis and treatment of serious and life-threatening ventricular arrhythmias. In 2007 it was withdrawn and discontinued for commercial reasons. Moricizine can be administered intravenously but was more commonly provided as an oral formulation.

Bepridil is a calcium channel blocker that has well characterized anti-anginal properties and known but poorly characterized type 1 anti-arrhythmic and anti-hypertensive properties. It has inhibitory effects on both the slow calcium and fast sodium inward currents in myocardial and vascular smooth muscle, interferes with calcium binding to calmodulin, and blocks both voltage and receptor operated calcium channels. It is used to treat hypertension (high blood pressure), angina (chest pain), sustained atrial fibrillation and tachyarrhythmia. The most common side effects were upper gastrointestinal complaints (nausea, dyspepsia or GI distress), diarrhea, dizziness, asthenia and nervousness. Certain drugs could increase the likelihood of potentially serious adverse effects with bepridil hydrochloride. In general, these are drugs that have one or more pharmacologic activities similar to bepridil hydrochloride, including anti-arrhythmic agents such as quinidine and procainamide, cardiac glycosides and tricyclic anti-depressants. Anti-arrhythmics and tricyclic anti-depressants could exaggerate the prolongation of the QT interval observed with bepridil hydrochloride. Cardiac glycosides could exaggerate the depression of AV nodal conduction observed with bepridil hydrochloride.

Indecainide, an antiarrhythmic agent classified as type IC. Class IC drugs greatly depress intracardiac conduction and are the most potent antiarrhythmic compounds able to suppress ventricular premature beats. Indecainide was used under brand name decabid for the treatment of life-threatening dysrhythmias and sustained ventricular tachycardia. However, that usage was discontinued. Indecainide have mediated the pharmacological actions through a blocking of Na+-channel.

Etidocaine, marketed under the trade name Duranest, is a local anesthetic given by injection during surgical procedures and labor and delivery. Etidocaine has a long duration of activity, and the main disadvantage of using during dentistry is increased bleeding during surgery. Etidocaine stabilizes the neuronal membrane by inhibiting the ionic fluxes required for the initiation and conduction of impulses, thereby effecting local anesthetic action.

Chlorphenesin carbamate (Maolate, Musil) is a centrally acting muscle relaxant used to treat muscle pain and spasms. Сhlorphenesin acts in the central nervous system (CNS) rather than directly on skeletal muscle. It also has antifungal and some antibacterial properties. The major adverse effects are drowsiness and dizziness.

Beta-carotene is found in many foods and is sold as a dietary supplement. Beta-carotene is a carotenoid, weak antioxidant; precursor of vitamin A, which is essential for vision and growth. Used to reduce the severity of photosensitivity reactions in patients with erythropoietic protoporphyria (EPP). Has been used in high-dose antioxidant supplements containing ascorbic acid and vitamin E with zinc in high-risk patients with age-related macular degeneration. Beta-carotene is also used to decrease asthma symptoms caused by exercise; to prevent certain cancers, heart disease, cataracts; and to treat AIDS, alcoholism, Alzheimer’s disease, depression, epilepsy, headache, heartburn, high blood pressure, infertility, Parkinson’s disease, rheumatoid arthritis, schizophrenia, and skin disorders including psoriasis and vitiligo.

Phenformin is a biguanide hypoglycemic agent with actions and uses similar to those of metformin. It activates AMP-activated protein kinase (AMPK) and inhibits mTORC1 signaling. Phenformin used for the treatment of diabetes. Phenformin was removed from the U.S. market 20 years ago because of a high incidence of lactic acidosis. Risk factors for the development of lactic acidosis include renal deficiency, hepatic disease, cardiac disease, and drug interaction such as cimetidine. Phenformin exerts potential anti-neoplastic action.