22994-85-0

Benznidazole is an orally bioavailable antiprotozoal agent. It is a 2-nitroimidazole prodrug that becomes active when the nitro group is reduced within the parasite. It inhibits the growth of the parasites T. cruzi, T. vaginalis, G. lamblia, and E. histolytica (IC₅₀s = 8.1, 18.62, 22.58, and 4.27 μM, respectively). It also inhibits clonogenic growth of human C33A cervical and KNS42 glioblastoma cancer cells under hypoxic, but not normoxic, conditions when used at a concentration of 100 μM. Benznidazole (100 mg/kg per day) decreases T. cruzi blood parasitemia to below detectable levels in a mouse model of chronic stable Chagas disease. Formulations containing benznidazole have been used in the treatment of Chagas disease caused by T. cruzi.

Benznidazole is the second of the drugs approved for treatment of Chagas' disease. Like nifurtimox, it is effective against the circulating form of Trypanosoma cruzi during the acute phase of the disease, but also like nifurtimox, it is ineffective during the chronic stage of the disease.

Benznidazole (BNZ) is traditionally used to treat Chagas disease caused by Trypanosoma cruzi. The drugs used for the treatment of this disease, Nifurtimox and Benznidazole, are toxic and present sever e side effects.

ChEBI: A monocarboxylic acid amide obtained by formal condensation of the carboxy group of (2-nitroimidazol-1-yl)acetic acid with the aromatic amino group of benzylamine. Used for treatment of Chagas disease.

It exhibits antiprotozoal activity, particularly against Trypanosoma cruzi.

A synthetic 2-nitroimidazole, formulated for oral administration. Solubility in water 400 mg/L.

Studies suggest that benznidazole does not catalyze the formation of ROS and, therefore, has a mechanism of action different from that of nifurtimox. It has been proposed that benznidazole undergoes an one-electron transfer to the nitro group, which in turn dismutates to give back the nitroimidazole and a nitrosoimidazole. The latter product may then undergo an electrophilic addition to trypanothione, which leads to depletion of trypanothione, an essential enzyme system in the Trypanosoma cruzi.

Oral bioavailability :High
Cmax 100 mg oral ：2.2–2.8 mg/L after 3–4 h
Plasma half-life：10.5–13.6 h
Volume of distribution：c. 0.56 L/kg
Plasma protein binding： c. 44%
The 2-nitro group undergoes reduction to the amine and hydrolysis to the hydroxy derivative.

Benznidazole is used in treatment of South American trypanosomiasis (Chagas disease).

N-Benzyl-2-nitroimidazole-1-acetamide (Radanil, Rochagan)is a nitroimidazole derivative that is used for the treatment ofChagas disease. It is not available in the United States but isused extensively in South America. The effectiveness of benznidazoleis similar to that of nifurtimox. Therapy forAmerican trypanosomiasis with oral benznidazole requiresseveral weeks and is frequently accompanied by adverse effectssuch as peripheral neuropathy, bone marrow depression,and allergic-type reactions.

Adverse effects are more common in the elderly and include nausea, vomiting, abdominal pain, peripheral neuropathy and severe skin reactions.

This SSRI antidepressant (FW = 260.25 g/mol; CAS 22994-85-0; Abbreviation: PXT), known by its trade name Aropax®, Paxil®, Pexeva®, Seroxat®, Sereupin® and Brisdelle® as well as its systematic name (3S,4R) - 3-[ (2H-1,3-benzodioxol-5-yloxy) methyl]-4- (4-fluorophenyl) piperidine, is a selective serotonin reuptake inhibitor (IC50 = 33 μM) that is indicated for the treatment of major depression, obsessive-compulsive disorder, panic disorder, posttraumatic stress disorder, generalized anxiety disorder and vasomotor symptoms, such as hot flashes and night sweats, that are associated with menopause (1-4). Significantly, Antidepressant responses to selective serotonin reuptake inhibitors (citalopram or paroxetine) are abolished in mice unable to synthesize histamine due to either targeted disruption of histidine decarboxylase gene (or HDC–/–) or injection of a- fluoromethylhistidine, a suicide inhibitor of this enzyme. Such findings demonstrate that SSRIs selectively require the integrity of the brain histamine system to exert their preclinical responses. (See also Citalopram; a-Fluoromethyl histidine) Pharmacokinetic Properties: Plasma concentration and time-curves fit a two-compartment open model, with the oral route giving a longer t1/2 (30 hours) than by the intravenous route (12 hours). Deviations probably reflect saturated elimination kinetics during first-pass metabolism. Co-administration of lipoic acid and PXT may improve anxiolytic and antidepressant responses, suggesting that PXT may deplete lipoic acid stores or that PXT interferes with some lipoic acid- requiring metabolic pathway. Somewhat surprisingly, Paroxetine (20-40 μM) induces growth inhibition and apoptosis in prostate cancer cells in vitro . Paroxetine is metabolized by CYP2D6 via demethylenation of the methylenedioxy group, yielding a catechol metabolite and formic acid. Paroxetine is also a potent inhibitor of cytochrome P450 2D6 (CYP2D6). Time- dependent inhibition was demonstra–t1ed with an apparent Ki of 4.8 μM and an apparent kinact value of 0.17 min. Paroxetine has critical but differential effects on IL-6 and TNFα production in macrophages and likely regulates their formation by different mechanisms. Key Pharmacokinetic Parameters: See Appendix II in Goodman & Gilman’s THE PHARMACOLOGICAL BASIS OF THERAPEUTICS, 12th Edition (Brunton, Chabner & Knollmann, eds.) McGraw-Hill Medical, New York.

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