Metabolites toxicity

Allemand H, Pessayre D, Descatoire V, et al. 1978. Metabolic activation of trichloroethylene into a chemically reactive metabolite toxic to the liver. J Pharmacol Exp Ther 204 714-723. 

Half-lives from 2-40 h oral activity Hepatic metabolism-some active metabolites Toxicity Extensions of CNS depressant effects dependence liability Interactions Additive CNS depression with ethanol and many other drugs... 

Imipramine Mixed and variable blockade of NET and SERT Like SNRIs plus significant blockade of autonomic nervous system and histamine receptors Major depression not responsive to other drugs chronic pain disorders incontinence obsessive-compulsive disorder (clomipramine) Long half-lives CYP substrates active metabolites Toxicity Anticholinergic, G.-blocking effects, sedation, weight gain, arrhythmias, and seizures in overdose Interactions CYP inducers and inhibitors... 

Nefazodone Inhibition of 5- 2 receptor nefazodone also blocks SERT weakly Trazodone forms a metabolite (m-cpp) that blocks 5-HT2A,2C receptors Major depression sedation and hypnosis (trazodone) Relatively short half-lives active metabolites Toxicity Modest receptor blockade (trazodone) Interactions Nefazodone inhibits CYP3A4... 

Since a detailed review of antibiotics is beyond the scope of this chapter, we focus on the recent works on microbial secondary metabolites toxic to animals. In addition, there are many reviews on herbicides produced by microbes3-5 and toxins of plant pathogenic fungi.6 7... 

The presence of secondary metabolites in organisms has been proposed as an adaptation against predation [56, 57, 58, 59, 60, 61]. Secondary metabolites, toxic or inhibitory to a range of predators, have been isolated from a whole host of different organisms. Secondary metabolites originating from such diverse organisms as dytiscid beetles, (62], tropical seaweeds [63], gorgonians [64. 65] and sea hares [66] have been shown to exhibit anti-predatory properties. 

However, loss reduction is not the sole aim of plant protection. Certain rust and smut fungi not only damage crops, but also produce metabolites toxic to human beings and domestic animals. The chitin shield of the grain weevil contains carcinogenic compounds, quinones, which may appear in the flour prepared from the infested cereal. 

The structural formulas of meperidine, a phenylpiperi-dine Meperidine is predominantly a p-receptor agonist, and it exerts its chief pharmacological action on the CNS and the neural elements in the bowel. It is no longer recommended for the treatment of chronic pain because of concerns over metabolite toxicity. It should not be used for longer than 48 hours or in doses greater than 600 mg/day. 

Smith DA, Obach RS, Williams DP, Park BK. Qearing the MIST (metabohtes in safety testing) of time The impact of duration of administration on drug metabolite toxicity. Chem Biol Interact 2009 179(1) 60 67. 

Docherty, K.M., Joyce, M.V, Kulacki, K.J. and Kulpa, C.F., Microbial biodegradation and metabolite toxicity of three pyridinium-based cation ionic liquids. Green Ghem.12, 701-712 (2010). 

L. (2010) Hydrolysis of benzonitrile herbicides by soil actinobacteria and metabolite toxicity. Biodegradation, 21, 761-770. 

Differences in phthalate structure determine how they are metabolized and their toxic effects. MBuP and MBzP, metabolites of DBP and BBzP, have been identified as active metabolites toxic to reproductive endpoints, including sperm concentration in adult males (Hauser et al. 2006). Direct measures of parent phthalates or phthalate monoester metabolites in blood are difficult to interpret because of the high likelihood of contamination from sampling or from lab materials given that esterase activity after sample collection can generate monoester metabolites in samples contaminated after collection (Calafat et al. 2013). 

Vesela A, Franc M, Pelantova H, Kubac D, Vejvoda V, ulc M, Bhalla T, Mackova M, Lovecka P, Jaml P, Demnerova K, Martinkova L. Hydrolysis of benzonitrile herbicides by soil actinobacteria and metabolite toxicity [J]. Biodegradation 2010, 21 (5) 761-770. 

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