Disease relevance of proadifen

• SKF 525-A, an inhibitor of mixed-function oxidase, produces in hepatoma microsomes a P-450 type I binding spectrum similar to that of hepatic microsomes [1].
• Further, the microsomal cytochrome P-450 inhibitor, SKF 525-A, 75 mg/kg body weight injected i.p. to mice 30 min prior to 4-CP administration, blocked the reduction of liver thiol content produced by 4-CP [2].
• Additionally, the toxicity of either BB or AA, evaluated at 4 hr, was inhibited when slices were preincubated for 30 min with beta-ethyl-2,2-diphenylvalerate hydrochloride (SKF 525-A) (0.1 mM) or pyrazole (1.0 mM), respectively [3].
• It is suggested that local anesthetic or 'class 1' action probably accounts for the antiarrhythmic effectiveness of SKF 525-A (7-20 mg/kg i.v.) in all four arrhythmia models and for perhexiline-induced increased FT and antagonism of CLA (15-20 mg/kg) [4].
• Proadifen (SKF-525 A, 50 mg/kg) injected i.p. 24 h and 1 h before and 24 h and 48 h after the injection with ethyl carbamate tended to decrease the multiplicity of lung adenomas, but not to a significant extent [5].

Psychiatry related information on proadifen

• On the other hand, in the case of the dose of 10 mg/kg of CGP 37849, SKF-525-A did not affect the locomotor activity, but enhanced the motor disturbance symptoms induced by this dose of CGP 37849 [6].

High impact information on proadifen

• The generation of all metabolites were inhibited by alpha-naphthoflavone and antiserum to NADPH-cytochrome P-450 reductase, whereas SKF 525-A had only a minimal effect [7].
• The biotransformation was inhibited by typical cytochrome P-450 inhibitors such as carbon monoxide, SKF 525-A, and metyrapone [8].
• These studies demonstrate that, like estradiol, SKF 525-A interacts with the estrogen receptor [9].
• Similar results were obtained with uteri from ovariectomized or ovariectomized and adrenalectomized rats, indicating that the action of SKF 525-A did not depend on the availability of ovarian or adrenal hormones [9].
• Several potential modifiers, including retinoic acid, indomethacin, 1,3-diamino-2-propranol, alpha-naphthoflavone, and SKF 525 A had unequal effects on ODC and AHH activities [10].

Chemical compound and disease context of proadifen

• The SKF 525-A and methimazole treatments selectively inhibited the formation of PTP and MPTP N-oxide, respectively, but had no significant effect on the rate and extent of MPTP toxicity [11].
• BHTOH was found to be considerably more toxic to Clara cells than BHT, and both toxicity and metabolism were simultaneously depressed by the cytochrome P450 inhibitor SKF 525-A [12].
• These mitochondrial mechanisms in paraquat toxicity seemed to be more probable in vivo than are microsomal mechanisms; the latter are postulated to function in detoxication because phenobarbital diminished paraquat toxicity and SKF 525-A or cobaltous ions enhanced the toxicity [13].
• Effect of adrenalectomy, pretreatment with SKF 525-A, phenobarbital and diethyl maleate on the acute toxicity of fenitrothion in male rats [14].
• The effects of microsomal enzyme inhibitors (7, 8-BF and SKF 525-A) on the S-9-mediated mutagenicity of o-, m- and p-phenylenediamine were investigated using Salmonella typhimurium TA98 [15].

Biological context of proadifen

• Tissue distribution of levo-methadone in nonpregnant and pregnant female and male mice: effect of SKF 525-A 1,2 [16].
• SKF 525-A or ethylmorphine inhibit lipid peroxidation of normal and tumor microsomes to the same extent (about 60%) [1].
• Both DMN demethylation and mutagenesis were inhibited by the addition of either SKF 525-A or benzo (a)pyrene to the reaction mixtures [17].
• Pretreatment of mice with the inducers phenobarbital and 3-Methylcholanthrene decreased the alkylation rates, while administration of the inhibitors SKF 525 A and CFT 1201 caused an increase [18].
• 3. Such a difference does not appear in the brain of mice treated with racemic amphetamine or in the brain of rats pre-treated with SKF 525-A, an inhibitor of amphetamine hydroxylation [19].

Anatomical context of proadifen

• In contrast, the reduced level of cytochrome P-450 in hepatic microsomes from rats pretreated with the SKF 525-A did not revert to the control value after dialysis [20].
• Heterogeneity of cytochrome P-450 in rat liver microsomes: selective interaction of metyrapone and SKF 525-A with different fractions of microsomal cytochrome P-450 [21].
• Drug-induced porphyrin biosynthesis--XIX. Potentiation of the porphyrin-inducing effects of SKF 525-A in the chick embryo liver by 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine, an antihibitor of ferrochelatase [22].
• A comparison of effects of SKF 525-A and procaine on excitation-contraction coupling in single crayfish muscle fibers [23].
• Pretreatment with SKF 525-A inhibited metabolism and increased the tissue levels of unchanged drug, however, even under these conditions storage in adipose tissues did not occur, the adipose storage index being still less than unity [24].

Associations of proadifen with other chemical compounds

• Other cytochrome P-450 inhibitors (cimetidine, SKF 525-A or piperonyl butoxide) given at this low molar dose (250 mumol X kg-1) exerted no protective effect [25].
• At the same pH, procaine blocked the contractions elicited by SKF 525-A, by high K media, by the graded electrogenesis and by caffeine, and converted the graded membrane responses into all-or-none spikes [23].
• The steady state concentration of this radical was not decreased by CO or SKF 525-A (two inhibitors of cytochrome P450), but was decreased by NADP+ (10 mM) or p-chloromercuribenzoate (0.47 mM) (two inhibitors of NADPH-cytochrome P450 reductase activity) [26].
• The formation of olefins required NADPH and it was inhibited by SKF 525-A, metyrapone, and carbon monoxide [27].
• In contrast, 16 alpha-hydroxylase activity in microsomes from SKF 525-A-induced rats, before and after dissociation with ferricyanide, was reduced by anti UT-A IgG to 32 and 19% of the respective uninhibited controls [28].

Gene context of proadifen

• Additionally, it was concluded that the "estrogenic" (uterotropic) activity observed in vivo [Calhoun et al. Proc. Soc. Exp. Biol. Med. 136:47 to 50 (1971)] with SKF 525-A, is mediated through the uterine estrogen receptor [9].
• The formation of MA6 was inhibited by SKF 525-A, suggesting that CYP plays role in the formation of MA6 [29].
• The cytochrome P-450 inhibitors SKF 525-A and 1-(2-isopropylphenyl)imidazole inhibited demethylation both in whole cells and in the enzyme preparation, though the latter compound was effective only at high concentrations [30].
• All the mice pretreated with CoCl(2) (a CYP synthesis inhibitor) or SKF 525-A (a CYP inhibitor) were dead after 5 days, and troleandomycin (a CYP3A-specific inhibitor) also reduced the survival rate [31].
• The inhibitors of cytochromes P-450, SKF 525-A and 1-aminobenzotriazol, produced 85 and 70% inhibitions of DCA formation, respectively [32].

Analytical, diagnostic and therapeutic context of proadifen

• SRII of morphine repeated after treatment SKF 525-A (20 mg/kg b. wt. intraportally) showed decreased recovery of morphine glucuronide (MG) in the bile and in the venous outflow [33].
• The electron microscopy of liver from SKF 525 A-treated animals, shows the presence of large areas of round vesicles of swollen endoplasmic reticulum, partly due to smooth component and part due to rough component, having detached the ribosomes from their membranes [34].
• Therefore, the inductive effects of SKF 525-A on CYP enzyme activities and proteins were investigated in female B6C3F1 mice to elucidate the potentiation of cocaine-induced immunosuppression by SKF 525-A [35].
• Meanwhile, when the type of isozyme induced by SKF 525-A was analyzed by Western immunoblotting with monospecific anti-CYP 1A and anti-CYP 2B antibodies, only the CYP 2B appeared to be induced [35].
• The low activity of amitriptyline seems to be mainly due to poor resorption, since pretreatment of the animals with SKF 525 A only slightly increased the potency whereas intraperitoneal injection of amitriptyline had a rather marked effect on the NA uptake (ED50 = 11 mg/kg intraperitoneally) [36].

References