Disease relevance of Benzodioxole

• The relationship between the metabolism and toxicity of benzodioxole compounds [1].
• Seven 1,3-benzodioxole derivatives have been found to be effective against certain types of experimentally induced arrhythmias [2].

High impact information on Benzodioxole

• It has been suggested that acenaphthylene (ACN), piperonyl butoxide (PBO) and other methylenedioxyphenyl (benzodioxole) compounds can function as aromatic hydrocarbon-responsive receptor (AHR)-independent inducers of the cytochrome P450 (CYP) 1A2 in mouse liver [3].
• P450 2B4 was 4-16-fold more active than 2B5 towards benzphetamine, 7-ethoxycoumarin, methylenedioxybenzene, and pentoxyresorufin [4].
• Antibodies against CYP2B4, but not those against CYP4B1, caused a marked inhibition of the demethylenation and aromatic hydroxylation of MDB [5].
• This is a potent antagonist, binding to the ETA and ETB receptor subtypes with affinities (IC50) of 0.4 and 520 nM, respectively, and also contains the aforementioned benzodioxole [6].
• The benzodioxole ((methylenedioxy)benzene) group is present in a number of endothelin (ET) receptor antagonists thus far reported [6].

Anatomical context of Benzodioxole

• However, the antibody to P-450d recognizes two new polypeptides (approximately 50K Mr) from sodium dodecyl sulfate-polyacrylamide gels of liver microsomes from BD-treated rats [7].
• However, the polypeptides could not be generated in vitro by addition of BD to 3-MC-induced microsomes with NADPH under conditions which produced spectral metabolite complexes, or in a reconstituted system with P-450d [7].

Associations of Benzodioxole with other chemical compounds

• The aromatic ring in MDB undergoes both demethylenation to catechol and aromatic hydroxylation to sesamol, whereas that in MDA undergoes only demethylenation to dihydroxyamphetamine [5].
• In contrast, BD is a phenobarbital-type inducer, increasing P-450b, but producing little or no increase in P-450c or P-450d [7].
• 2. Stiripentol, an antiepileptic drug containing a methylenedioxybenzene moiety, proved to be a potent inhibitor of the reaction, with an IC50 value close to 1 microM under the conditions of study and without preincubation [8].

Gene context of Benzodioxole

• The beta-1, beta-2 and beta-3 adrenergic properties of several benzodioxole-containing phenethanolamines were determined in vitro in both functional and binding assays [9].
• They are intensified by coadministration of 3-MC with BD and may represent either modified isozyme-metabolite adducts or degradation products of P-450d [7].
• BBD, but not MBBD and DBBD, induced cytochrome P-450 and formed a Type III metabolite-cytochrome P-450 complex, in vitro and in vivo [10].

References