Disease relevance of proadifen

• We reasoned that, if the influx of extracellular calcium mediated the hypoxic mechanism, pressor responses to alveolar hypoxia (2.5% O2) would be susceptible to inhibition by the calcium antagonists verapamil (2 X 10(-5) to 2 X 10(-1) mM) and SKF 525A (2.6 to 260 mM) [1].
• Treatment with SKF 525A, piperonyl butoxide, or 1-benzylimidazole, followed by a single 200 mg/kg dose of cyclophosphamide, did not diminish pulmonary thymidine incorporation (an index of cell division after injury) or hydroxyproline content (an indicator of fibrosis), compared to mice treated with cyclophosphamide alone [2].
• MPP(+)-induced toxicity was abolished by pretreatment of the slices with inhibitors of monoamine oxidase (MAO; pargyline and deprenyl) or inhibitors of P450 (piperonyl butoxide or SKF-525A) or dopamine uptake blocker (GBR-12909), as measured by the activity of NADH-DH in slices and leakage of lactate dehydrogenase from the slice into the medium [3].
• SKF-525A treatment plus THC produced 36% cleft palates [4].
• Proadifen-treatment and Nx had no significant effect on the duration of the hypotension in control rats or in L-NAME-treated rats [5].

Psychiatry related information on proadifen

• The anticonvulsant properties of PRM, PB, and PEMA against maximal electroshock in mice were also studied with the use of the metabolic inhibitor SKF 525A [6].
• Pretreatment of rats with SKF-525A and CCl4 also resulted in the enhancement of methamphetamine-induced stereotyped behavior [7].
• Effect of food deprivation, phenobarbital, and SKF-525A on teratogenicity induced by 2-sec-butyl-4,6-dinitrophenol (dinoseb) and on disposition of [14C]dinoseb in mice [8].

High impact information on proadifen

• The effect of carbon tetrachloride (CCl4) on hepatocytes was substantially reduced by prior treatment with SKF 525A, an inhibitor of cytochrome P-450, and by exposure to the reducing reagent beta-mercaptoethanol [9].
• The LTB4 omega-hydroxylase was inhibited significantly by carbon monoxide, ferricytochrome c, SKF-525A, and Triton X-100, but was not affected by alpha-naphthoflavone, azide, cyanide, catalase, and superoxide dismutase [10].
• ACh-induced CD increases resistant to L-NAME and indomethacin were reduced after the administration of intracoronary quinacrine, an inhibitor of phospholipase A2, or proadifen, an inhibitor of cytochrome P-450 [11].
• During proadifen-inhibited 42K efflux, exogenous K+ augmented overflow of 3HNE, indicating that proadifen relaxed the hypoxic artery primarily by inhibiting K+-dependent exocytosis of NE [12].
• Because the inhibitory effects of PB on GJ intercellular communication are prevented by the nonspecific cytochrome P-450 inhibitor SKF-525A (J. E. Klauning, et al., Toxicol. Appl. Pharmacol., 102: 533-563, 1990), we investigated whether alterations in Cx32 are coincident with changes in the major PB-inducible cytochrome P-450, termed b/e or IIB1/2 [13].

Chemical compound and disease context of proadifen

• Toxicity required cytochrome P-450 and NADPH, and was inhibited by SKF 525A [14].
• Pretreatment with the cytochrome P450 inhibitors cimetidine (200 mg/kg, i.p., in divided doses) or SKF 525A (50 mg/kg, i.p.) diminished toxicity [15].
• To evaluate the role of metabolism in the toxicity of papaver, cells were pretreated with SKF-525A or benzyl imidazole (cytochrome P450 system inhibitors) for 24 hr at 1 x 10(-5) or 1 x 10(-4) M, respectively, or with phenobarbital sodium (cytochrome P450 system inducer) for 3 days at 2 x 10(-3) M [16].
• Pretreatment of mice with SKF 525A or cobaltous chloride, two different types of inhibitors of the drug metabolizing system, afforded a marked protection against tyrosine toxicity [17].
• Pretreatment with cytochrome P450 inhibitors, such as SKF-525A (SKF), ketoconazole and 2-methy-1,2-di-3-pyridyl-1-propanone, enhanced the hepatocyte toxicity induced by DMNQ but did not affect BQ-induced hepatocyte toxicity [18].

Biological context of proadifen

• Amphenone B and SKF-525A, inhibitors of cytochrome P-450, strongly inhibit both NADPH- and cumene hydroperoxide-dependent lipid peroxidation [19].
• SKF-525A was used to examine cytochrome P450 contributions to the biotransformation of NNK [20].
• The ability of acetone to enhance and compound SKF 525A to inhibit microsomal aniline hydroxylation was decreased by the administration of all three alcohols [21].
• The inhibition by the cytochrome P450 inhibitor SKF-525A of the NO synthase activity in these subcellular fractions (IC50 = 90 microM) and the fact that mammalian cytochrome P450 enzymes are endoplasmic reticulum-bound proteins support the notion that the cerebellar NO synthase is a cytochrome P450-type hemoprotein [22].
• From the crystal and molecular structure, it is seen that SKF-525A has two principal modes of complementary interactions with the enzyme available: polar and non-polar [23].

Anatomical context of proadifen

• Conversion of 1.0 microM 20-CHO-LTB4 to 20-COOH-LTB4 by PMN microsomes was also dependent on NADPH and inhibited by antibody to cytochrome P-450 reductase, 1.0 mM SKF-525A, or 5.0 microM LTB5, indicating that this reaction was also catalyzed by cytochrome P-450LTB [24].
• SKF-525A inhibited these reactions by 63-74% in lung microsomes and 90-96% in liver microsomes [25].
• In isolated liver cells, SKF 525A (beta-diethylaminoethyl-2,2-diphenylpentanoate; an inhibitor of hepatic mixed function oxidase) could increase levels of unmetabolized EE2, cytosol receptor deletion, and nuclear receptor accumulation [26].
• In indomethacin- and L-NA-treated arteries, acetylcholine induced a smooth muscle hyperpolarization, which was blocked by SKF 525A (3 +/- 1 mV vs. 15 +/- 2 mV of control) [27].
• The ET(B)-mediated relaxations were endothelium dependent and inhibited by the nitric oxide synthase inhibitor N-nitro-l-arginine, the cytochrome P450 inhibitor SKF 525A, and high extracellular K(+), but not by the cyclooxygenase inhibitor indomethacin [28].

Associations of proadifen with other chemical compounds

• Coincubation of the hepatocytes with the P450 inhibitors, metyrapone and SK&F 525-A, strongly protected against MMC-induced LDH leakage, GSH depletion, and LPO [29].
• The effect of pre-treatment with phenobarbitone (80 mg/kg i.p., daily for three days) or proadifen (SKF-525A, 50 mg/kg i.p., single dose) on the MAO-B inhibitory potency of (-)-deprenyl was also studied [30].
• Butylated hydroxyanisole also inhibited the reaction, whereas SKF-525A and metyrapone, which are inhibitors of cytochrome P-450-dependent N-dealkylation, did not [31].
• NADPH-dependent bioreduction of 15 to its ketone metabolite 16 was located in the microsomal fraction and inhibited by SKF-525A and pCMBA [32].
• 4. The desensitization of ACh receptors potentiated by proadifen, prevented completely the 6- to 8-fold prolongation of EPC which was induced by neostigmine inhibition of synaptic AChE [33].

Gene context of proadifen

• Carbon monoxide, SKF-525A, metyrapone, and benzylimidazole strongly inhibited N-demethylation and 4-hydroxylation, indicating the participation of P-450 monooxygenase in these reactions [34].
• However, SKF-525A was ineffective against the effect of LPS alone on liver and blood GPx and CAT or on hepatic GSH and GRx, suggesting that these effects were not mediated by cytochrome P450 oxidative metabolism [35].
• In contrast, SKF-525A weakly inhibited CYP1A2-dependent activities (46% inhibition at 1200 microM) and CYP2E1-dependent activities (65% inhibition at 1000 microM) [36].
• Daily SKF-525A pretreatment at a dose of 30 mg/kg, i.p., for 7 days 1 hour prior to KET and COC in combination effectively reversed the effects of this combination on body weight, organ/bodyweight ratios, histopathology, and serum IgM and IL-10 concentrations without affecting leukocytic counts [37].
• In contrast, we observed that CYP450 inhibitors such as SKF-525A, 17-octadecynoic acid, 1-aminobenzotriazole, and 6-(2-propargyloxyphenyl)hexanoic acid reduced 12(S)-HETE levels, 3T6 fibroblast growth, and DNA synthesis induced by FBS [38].

Analytical, diagnostic and therapeutic context of proadifen

• Cytochrome P-450-dependent AA metabolites (those whose formation required NADPH, were inhibited by SKF-525A, but not by indomethacin) were separated by thin-layer chromatography and high-pressure liquid chromatography (HPLC) [39].
• 2. The rats were pretreated with the NO-synthase inhibitor, N omega-nitro-L-arginine methyl esther (L-NAME) (0.3 g kg-1), proadifen (50 mg kg-1), an inhibitor of the medullipin-system, and nephrectomy (24 h) (Nx) alone, and L-NAME in combination with proadifen, Nx or phentolamine (2 mg kg-1) [5].
• Metabolism of monocrotaline was faster in livers from male rats than female rats, was inducible with phenobarbital pretreatment, and was inhibited by coperfusion with the P-450 mixed-function oxidase inhibitor SKF-525A, anoxic perfusion conditions, and low temperatures [40].
• Premedication with SKF-525A, an inhibitor of drug-metabolizing enzymes, significantly prolonged the t1/2 of Imip, while at the same time production of DMI from Imip was accordingly inhibited [41].
• Pharmacokinetics of baicalin in rats and its interactions with cyclosporin A, quinidine and SKF-525A: a microdialysis study [42].

References