Disease relevance of Zoxazolamine

• The results of this experiment suggest that the addition of zoxazolamine to the diet may prolong the survival and reduce the incidence of right ventricular hypertrophy and hypertensive pulmonary vascular disease in male rats given a single subcutaneous injection of monocrotaline [1].
• The purpose of this investigation was to determine whether the pharmacodynamics of the centrally acting skeletal muscle relaxants zoxazolamine (ZOX) and chlorzoxazone (CZX) are altered in renal failure [2].
• Kinetics of drug action in disease states. XXXV: Effect of hypovolemia on the pharmacodynamics of zoxazolamine in rats [3].
• Fasting also increased DEN-dependent centrilobular cell necrosis and specifically drug metabolism as indicated in vivo by a decreased time of paralysis of the lower limbs induced by zoxazolamine (40 mg/kg body weight, ip) and by an unaltered sleeping time induced by sodium pentobarbital (40 mg/kg body weight, ip) [4].
• Finally, carrageenan edema, a model of acute inflammation, did not affect barbiturate sleeping times of zoxazolamine paralysis, nor were any of these drugs studied more lethal in this disease state [5].

High impact information on Zoxazolamine

• These animals also show decreased metabolism of the classic CYP substrate zoxazolamine and a complete loss of the liver hypertrophic and hyperplastic responses to these inducers [6].
• The metabolism of zoxazolamine to 6-hydroxyzoxazolamine by liver microsomes from neonatal rats is stimulated severalfold by the in vitro addition of flavone, a naturally occurring compound found in several plant species [7].
• Backcross progeny were tested for Ah genotype by zoxazolamine sleeping time [8].
• 7,8-Benzoflavone also increased the rates of hydroxylation of zoxazolamine and antipyrine at 10(-4) M but inhibited these reactions at 10(-6) M [9].
• The effects of 7,8-benzoflavone on the hydroxylation of benzo[a]pyrene and zoxazolamine in microsomes from human liver were similar to those in homogenates [9].

Chemical compound and disease context of Zoxazolamine

• Depression of the hepatic microsomal enzyme system(s) in adjuvant-induced polyarthritis (AIP), a chronic inflammation model, has been confirmed indirectly by the enhancement of hexobarbital Na-induced sleeping time and extended for the first time to zoxazolamine-induced paralysis [5].
• A series of benzazole-related, centrally acting muscle relaxants, comprising benzimidazole, chlorzoxazone, and zoxazolamine, were found to give substantial protection against the tremors and convulsions associated with the high pressure neurologic syndrome (HPNS) in the mouse [10].
• Effects of cimetidine on theophylline, acetaminophen, and zoxazolamine toxicity in the intact mouse [11].

Biological context of Zoxazolamine

• Comparison of the hydroxylation of zoxazolamine and benzo[a]pyrene in human placenta: effect of cigarette smoking [12].
• Ahr phenotype was determined by the zoxazolamine sleeping time test after beta-naphthoflavone pretreatment at 6 weeks of age [13].
• Previous experiments had shown that carbon monoxide inhalation prolonged the in vivo response zoxazolamine [14].
• Dose-dependent pharmacokinetics of zoxazolamine in the rat [15].
• Cigarette smoke did not induce statistically significant alterations in hepatic enzyme activity when measured in vivo (pentobarbital sleep time and zoxazolamine paralysis time) or in vitro (oxidation, hydrolysis, glucuronidation, and glutathione conjugation) [16].

Anatomical context of Zoxazolamine

• A 59-fold range in benzo[a]pyrene hydroxylase activity and a 28-fold range in zoxazolamine hydroxylase activity were found in the placentas of cigarette smokers [12].
• Pyruvate supplementation did not alter hexobarbital sleep time or zoxazolamine paralysis time, two in vivo measures of microsomal mixed-function oxidase activity, and the disposition of radioactivity in plasma or sciatic nerve following subcutaneous injection of [14C]acrylamide [17].
• Binding of 20 nM [3H]-glycine to cortical synaptosomal membranes was inhibited by (+)-HA-966, IC50 = 3.16 microM, but only poorly by zoxazolamine, IC50 V 474 microM, and chlorzoxazone, a related drug, caused no displacement [18].
• Pretreatment with PCN (an inducer of hepatic microsomal enzymes) or ACTH (known to alter protein binding and excretion of zoxazolamine) shortened paralysis in thymectomized animals; but only in comparison to thymus ablated controls [19].

Associations of Zoxazolamine with other chemical compounds

• Flavone stimulated zoxazolamine metabolism both in vitro and in vivo when control or phenobarbital-treated rats were used, but flavone inhibited the in vitro and in vivo hydroxylation of zoxazolamine when rats induced with 5,6-benzoflavone were studied [20].
• The in vitro addition of the hydroxylated flavonoids apigenin, chrysin, fisetin, morin and quercetin inhibited the hydroxylation of zoxazolamine by liver microsomes from neonatal rats, but studies with quercetin and apigenin indicated that these flavonoids had no effect on the in vivo metabolism of zoxazolamine [20].
• The effects of itraconazole, a triazole antifungal agent, on cytochrome P450 were investigated by measuring the anti-convulsant activity of phenytoin in mice, and zoxazolamine paralysis time, tolbutamide clearance, and plasma dicoumarol concentrations after a single injection of dicoumarol, in rats [21].
• In vitro drug metabolism studies with hexobarbital and zoxazolamine as substrates confirmed the post-traumatic depression of the cytochrome P-450-catalyzed oxidation of these drugs which was suggested by previous in vivo pharmacokinetic studies [22].
• The effects of aging on ethanol inhibition of zoxazolamine metabolism in vitro and in vivo were studied in female Fischer 344 rats aged 4, 14 and 26 months [23].

Gene context of Zoxazolamine

• Furthermore, we determined that the D2.B6N-Asp1b mouse expresses both the D2 phenotype and genotype at the Ahr locus, i.e., zoxazolamine paralysis and T to C and G to A transition mutations in the Ahr cDNA at bp sites 3330 and 3336, respectively [24].
• Ginsan in the dose of 100 mg/kg caused marked elevation (1.7 to approximately 2 fold) of HO activity, decrease of total CYP450 level (by 20-34%), and prolongation of zoxazolamine-induced paralysis time (by 65-70%), and showed some differences between male and female mice [25].
• Several derivatives of dipyrido[1,2-a:3',2'-d]imidazole related to protein pyrolysates have been studied for their effects on the P-450 system of hepatic parenchyma and two dependent monoxidase enzymes, zoxazolamine hydroxylase and dimethylnitrosamine-N-demethylase (DMN-d-ase) [26].
• A highly sensitive radiometric assay for zoxazolamine hydroxylation by liver microsomal cytochrome P-450 and P-448: properties of the membrane-bound and purified reconstituted system [27].
• Zoxazolamine paralysis times, an in vivo marker of CYP1A1 activity, were reduced from 184 +/- 18 min in saline-treated rats to 103 +/- 12.5 min 24 hr after a single 1.7-mg ODN1 iv injection [28].

Analytical, diagnostic and therapeutic context of Zoxazolamine

• The intraperitoneal injection of flavone into neonatal rats causes an immediate several-fold stimulation in the rate of total body metabolism of simultaneously administered zoxazolamine [7].
• Both ETOH and INH also increased zoxazolamine 6-hydroxylation but, in contrast to other rodent species, this drug-metabolizing activity was decreased in hamster liver microsomes after treatment with either PB or BF [29].
• Hepatotoxicity was documented by elevated serum glutamicpyruvic transaminase (SGPT) activity, by histologic evaluation of the extent of cellular necrosis, by electron microscopy of the mitochondrial fraction, and by the increased duration of zoxazolamine-induced paralysis [30].
• Thymectomy performed at least 24 hr before injection of zoxazolamine significantly prolonges paralysis time [19].

References