cardiac toxicity

Levobupivacaine hydrochloride ((S)-(-)-Bupivacaine monohydrochloride) is a reversible neuronal sodium channel inhibitor and the pure S(-)-enantiomer of bupivacaine, used as a long-acting local anesthetic.

(S)-Carvedilol is a non-selective β α-1 blocker.It exerts protection against the vascular or cardiac toxicity of Doxorubicin (DOX).

Levobupivacaine is an amino-amide local anaesthetic drug belonging to the family of n-alkylsubstituted pipecoloxylidide. It is the S-enantiomer of bupivacaine. Levobupivacaine hydrochloride is commonly marketed by AstraZeneca under the trade name Chirocaine. Compared to bupivacaine, levobupivacaine is associated with less vasodilation and has a longer duration of action. It is approximately 13 per cent less potent (by molarity) than racemic bupivacaine.Levobupivacaine is indicated for local anaesthesia including infiltration, nerve block, ophthalmic, epidural and intrathecal anaesthesia in adults; and infiltration analgesia in children. Adverse drug reactions (ADRs) are rare when it is administered correctly. Most ADRs relate to administration technique (resulting in systemic exposure) or pharmacological effects of anesthesia, however allergic reactions can rarely occur.

Uridine triacetate (RG 2133 triacetate) (Tri-O-acetyl uridine), an orally active prodrug of uridine, is efficiently absorbed in the gut and swiftly deacetylated in the circulation to release free uridine. It is utilized in the research of 5-fluorouracil (5-FU) and capecitabine toxicity, particularly targeting early-onset cardiac or central nervous system (CNS) complications.

O-Desmethyl Quinidine is a novel quinidine analog with significant antiarrhythmic activity and low acute toxicity that may be useful in the treatment of cardiac arrhythmias.

(R)-Carvedilol is a non-selective blocker of β α-1. (R)-Carvedilol exerts protection against the vascular or cardiac toxicity of Doxorubicin (DOX).

Halofantrine hydrochloride (SKF-102886) is an orally administered antimalarial drug effective against drug-resistant P. falciparum and P. vivax. SKF-102886 has cardiac toxicity, inhibiting hERG and delayed rectifier potassium channel I Kr, leading to prolonged QTc and PR intervals.

Quizalofop, a chlorophenoxy and phenoxy herbicide, selectively controls grasses via acetyl-CoA-carboxylase inhibition. While widely used in agriculture, Quizalofop has been associated with developmental and cardiac toxicity in zebrafish embryos.

Autotaxin-IN-7 (45) is a pyridine-2-carboxylic acid derivative exhibiting sub-nanomolar inhibition of ATX (IC50 = 0.086 nM) and features excellent cardiac safety (hERG > 30 μM) with minimal toxicity to fibroblasts. It inhibits the TGF-β/Smad signaling pathway, reducing α-smooth muscle actin (α-SMA) and extracellular matrix components (ECM). Autotaxin-IN-7 (45) can be used in pulmonary fibrosis research.

NMDAR antagonist 5 (Compound A17) is a multi-target antagonist that acts on NMDAR and monoamine transporters (SERT, DAT, and NET). It demonstrates strong NMDAR antagonistic efficacy (IC50= 0.3 μM) and effective activity on monoamine transporters (SERT IC50= 1.1 μM, DAT IC50= 0.7 μM, NET IC50= 2.7 μM). NMDAR antagonist 5 exhibits high safety with low toxicity (hepatic and renal toxicity IC50> 100 μM; cardiac toxicity IC50= 24.5 μM). It has antidepressant properties and is useful for depression research.

TK-129 is an orally active, potent inhibitor of KDM5B with an IC50 of 44 nM and is low-toxicity. TK-129 exhibits cardioprotective effects by inhibiting KDM5B and blocking the KDM5B-associated Wnt pathway. TK-129 can be used in cardiovascular disease studies to reduce isoprenaline-induced myocardial remodelling and fibrosis in vivo, as well as to reduce ang II-induced activation of cardiac fibroblasts in vitro [1].

(Rac)-Nebivolol ((Rac)-R 065824) is a racemic isomer of Nebivolol, a selective β1-adrenergic receptor antagonist (IC50 = 0.8 nM). Nebivolol exhibits vasodilatory activity and can prevent Nox2 NADPH oxidase up-regulation and lipoperoxidation in early stages of ethanol-induced cardiac toxicity.

Amrubicin, also known as SM-5887, is an anthracycline used in the treatment of lung cancer. Amrubicin intercalates into DNA and inhibits the activity of topoisomerase II, resulting in inhibition of DNA replication, and RNA and protein synthesis, followed by cell growth inhibition and cell death. This agent has demonstrated a higher level of anti-tumor activity than conventional anthracycline drugs without exhibiting any indication of the cumulative cardiac toxicity common to this class of compounds. It is marketed in Japan since 2002 by Sumitomo Pharmaceuticals.

Polystyrene microplastics (PS-MPs) are a toxic substance that poses risks to aquatic life, specifically causing cardiac harm to zebrafish and inducing male reproductive toxicity in mice [1] [2].

Antitubercular Agent-38, a derivative of Benzothiazinones (BTZs), demonstrates potent antituberculosis activity while maintaining low cardiac toxicity and minimal cell cytotoxicity [1]. This orally active compound is a promising therapeutic in the treatment of tuberculosis.

Fasciculin-I, a toxin isolated from mamba venom, exerts its toxicity primarily by inhibiting acetylcholinesterase (AChE). Additionally, it impedes the action of α-neurotoxins on nicotinic acetylcholine receptors and neutralizes cardiac toxins that interact with cell membranes [1].

Zofenoprilat, an angiotensin-converting enzyme (ACE; IC50 = 8 nM for rabbit lung enzyme) inhibitor and the active metabolite of the prodrug zofenopril, effectively counters angiotensin I- or bradykinin-induced contractions in isolated guinea pig ileum (EC50s = 3 and 1 nM, respectively). At a concentration of 10 nM, Zofenoprilat not only diminishes basal endothelin-1 secretion and nitric oxide (NO) production but also safeguards against TNF-α-stimulated increases in reactive oxygen species (ROS) and reductions in glutathione (GSH) levels within human umbilical vein endothelial cells (HUVECs). Furthermore, at 10 µM, it delivers protection to primary human cardiac microvascular endothelial cells from doxorubicin-induced toxicity and enhances hydrogen sulfide (H2S) production, along with the adhesion, migration, and proliferation of HUVECs. Additionally, Zofenoprilat (400 µM) mitigates end diastolic pressure and lactate dehydrogenase (LDH) release, demonstrating therapeutic potential in a Langendorff isolated perfused rat heart model of ischemia-reperfusion injury.

LSD1-IN-34 (Compound 7d) is an orally effective inhibitor of lysine-specific demethylase (LSD) and monoamine oxidase (MAO), exhibiting IC50 values of 4.51 nM for LSD1 and 18.46 nM for MAO A. This compound inhibits activation of neonatal rat cardiac fibroblasts (NRCF) induced by angiotensin II (Ang II) and shows no significant toxicity at 20 μM. LSD1-IN-34 also inhibits the TGFβ Smad signaling pathway, contributing to the improvement of heart failure in mice. Moreover, it demonstrates favorable pharmacokinetic properties in rats.