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Untitled document 89497283/7337

Date: 24 Aug 1994
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Page 51: pit35a00
08/24/94 Page -54- Effects of Ro15-4513 and other benzodiazepine receptor inverse agonists on alcohol -induced intoxication in the rat. By Suzdak PD; Paul SM; Crawley JN In English J Pharrnacol Exp Ther, "'(1988)"' . Vol. 24.5, No. 3, pp. 880-6. lournal code: lP3. lSSN: 0022-3565. [88:70463 TDXLINE] ABSTRACT> The ability of the imidazobenzodiazepine Ro15-4513 to antagonize the behavioral intoxication produced by ethanol and related short-chain alcohols was examined in the rat. Ro15-4513 dose dependently (0.5-10 mg/Ig i.p.: ICSO, 1.5 mg/kg) inhibited the intoxication induced by ethanol (2 g/kg), as well as t- amyl alcohol (0.36 g/kg) an methanol (4.66 g/kg. The effects of Ro15-4513 in blocking ethanol- induced intoxication were blocked by the benzodiazepine receptor antagonists Ro15-1788 and CGS-8216. However, Ro15-4513 was ineffective in antagonizing the intoxication observed after higher doses of ethanol (4 g/kg). In contrast, ethanol-induced intoxication was not antagonized by the benzodiazepine receptor antagonists Ro15- 1788 (10 mg/kg) or CGS-8216 (20 mg/kg), nor by the inverse agonists FG-7142 (10-30 mg/kg) or beta CCE (10 mg/I.g). When administered after ethanol, Ro15-4513 also reversed ethanol-induced intoxication in a dose-dependent manner (2.5-10 mg/kg i.p.: IC50, 5 mg/kg), an effect which was also blocked by Ro15-1788 and CGS-8216. However, neither beta CCE (10 mg/kg) or FG-7142 (less than or equal to 30 mg/ kg) alone reversed ethanol-induced intoxication. Moreover, beta CCE ( 10 mg/kg), when administered just befo:re Ro15-4513, completely antagonized the actions of Ro15-4513 in reversing ethanol-induced intoxication. These data suggest that the ability of Ro15-4513 0 antagonize, and to reverse, ethanol-induced intoxication is mediated via central benz.odiazepine receptors.(ABSTRACT TRUNCATED AT 250 WORDS) QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS IN A SERIES OF ALCOHOLS L11 EXHIBITING INHIBITION OF CYTOCHROME P-450-MEDIATED ANILINE HYDROXYLATION. By LEWIS D FV In English CHEM-BIOL INTERACT, "'(1987)"•• . Vo1. 62, No. 3, pp. 271-280. CODEN: CBINA. [88:12444 TOXLINE] ABSTRACT> BIOSIS COPYRIGHT: BIOL ABS. RRM ALCOF"OL TOXICITY ENVIRONMENTAL MEMBRANE BINDING ELECTRON STRUCTURE HYDROPHOBICITY MOLECULAR ORBITAL MARINE LIFE 05
Page 52: pit35a00
08/24/94 Page -40- Diffusion coefficients in a water/sodium dodecyl sulfate/ pentanol microemulsion base and its ammonium hydroxide analog. By Skurtveit R; Sjoblom J; Friberg SE; Yang CC; Ahmed AU In English J. Disper. Sci. Tech, *•*(1993)*** . Vol. 14, No. 6, pp. 68`'-702 ( REF 41). CODEN: JDTED. [94:44425 T3XLINE] ABSTRACT> IPA COPYRIGH: ASHP Self-diffusin coefficients were determined in sodium lauryl sulfate (sodium dodecyl sulfate)/pentyl alcohol ( pentanol) solutions with water and an aqueous concentrated ammonium hydroxide solution using nuclear magnetic resonance (NMR). Replacing water by the ammonium hydroxide solution destabilized the liquid crystalline phase in the system and also reduced the size of the colloidal association structures in the isotropic liquid part. SMALL-SCALE CHROMATOGRAPHY USED FOR MEASURING C-1-C-5 ALCOHOLS IN BLOO URINE. By IZOTOVA VI; KRASNOVA RR; SALOMATIN EM; SILAEVA IA; CHICHUEV YU A; YANOVSKII SM In Russian SUDEBNO-MEDITSlNSKAYA EKSPERTIZA, ***(193)'*• - Vol. 36, No. 3, pp. 27-31. CODEN: SMEZA. [94:24755 TDXLINE] ABSTRACT> BIOSIS COPYRIGHT: BIOL ABS. RRM RESEARCH ARTICLE HUMAN ETHANOL ORGANIC SOLVENTS FORENSICS STATISTICAL ANALYSIS ANALYTICAL METHOD A quantitative structure-activity relationship for the effect of alcohols on neutral red retention by the marine macroalga Enteromorpha intestinalis. By SCHILD R; DONKIN P; COTSIFIS PA; DONKIN ME In English CHEMOSPHERE, ***(7993)`* . Vol. 27, No. 9, pp. 1777-7788. CODEN: CMSHA. [94:17058 TOXLINE] ABSTRACT> BIOSIS COPYRIGHT: BIOL ABS. The effect of alcohols on the retention of neutral red, a vital stain, was investigated for the marine macroalga Enteromorpha intestinalis. The algae were incubated for 24 hrs in a series of ion-specific narcotic alcohols, and subsequently exposed to a neutral red solution for 3 hrs. On removal, the stain was extracted into a solvent and the resultant absorbance measured spectrophotometrically. EC50 values for the inhibition of neutral red uptake were used to establish a quantitative structure activity relationship (QSAR). This technique is reproducible and sensitive enugh for laboratory testing. Comparisons are made between this assay and others.
Page 53: pit35a00
08/24/94 Page -51- ESR analysis with long-chain alkyl spin labels in bovine blood platelets: Relationship between the increase in membrane fluidity by alcohols and phenolic compounds and their inhibitory effects on aggregation. By KITAGAWA S; KAMETANI F; TSUCHIYA K; SAKJRAI H In English BIOCHIM BIOPHYS ACTA, "'(1990)" . Vol. 1027, No. 2, pp. 123-129. CODEN:BBACA. [90:104184 TOXLINE[ ABSTRACT> BIOSIS COPYRIGHT: BIOL ABS. Four spin-labcled probes (5-doxylstearic acid (5-NS), its methly ester (5-NMS), 16-doxylmethylsterate (16- NMSO and 4-(N,N-dimethyl-N- pentdecyl)ammonium-2,2,6,6- tetrame[hylpiperidine-l-oxyl (CAT-15)) were used to monitor membrane fluidity change in bovine platelets induced by three alkyl alcohols, benzyl alcohol and two phenolic compounds. The relationship between the increase in membrane fluidity induced by these compounds and their inhibitory effects on platelet aggregation was observed. Experiments with the four probes showed that n-hexyl alcohol induced decruases in the order paramter of 5-NS and apparent rotational correlation times of the other probes at the same minimal alcohol concentration. The decreases were observed in the concentration range that inhibited aggregation. n- Amyl alcohol and n-butyl alcohol decreased the values of the parametes of the above mentioned only at higher concentrations that were dependent on their hydrophobicities. Like alkyl alcohols, benzyl alcohol and phenolic compounds decreased the values of the parameters in the concentration ranges in which these compounds inhibited platelet aggregation. The concentration of these compounds causing 50% inhibition of platelet aggregation, the IC50 values, and data on 5- NS-labeled platelets indicated that they inhibited aggregation and decreased the valte of the order parameter at lower concentrations relative to their Poct values in comparison to the effective concentrations of alcohols. Phenolic compounds also decreased the values of the apparent rotational correlation times of 5-NMS and 16- NMS. These results indicate that the inhibition of platelet aggregation by alcohols and phenolic compounds is due to membrane perturbation in wide range in depths within the lipid bilayer.
Page 54: pit35a00
08/24/94 Page -45- Competitive effect in bi-solute adsorption onto activated carbon: DSS, alcohols and phenols as solutes. By YAACOUBI A; MAZET M; DUSART 0 In French WATER RES, "'(799I)•'. Vol. 25, No. 8, pp. 929-938. CODEN: WATRA. [91:209795 TOXLINE] ABSTRACT> BIOSIS COPYRIGHTBIOL ABS. Many organic: toxic compounds in water supplies are resistant to conventional treatment. For low concentrations of organic contaminants, activated carbon is a good adsorbent ancc its use for water supplies has been widely studied. Bath experiments are generally used for the prediction of performance such as adsorptive capacity of granular activated carbon filters. To simulate the adsorption process, studies have been ctrried out with alcohols (Abe et al., 1979, 1980; Gaid et al., 1983; Belfort, 19 -.vith another organic solute, LaFrance et at. ( 1983), Dusart et al. (1990), Martin and Albahrani (1977, 1979) have investigated equilibrium expressions and different constants for multisolute absorption on activated carbon. The Frupose of this work is to study the adsorption kinetic evolution for sodium dodecylsulphate in the presence of n-alcohols (methanol to pentanol) and n-dodecanol and to examine the steric hindrance influence for the adsorption equilibrium pararieters and the external mass transfer coefficient Kf (equation (1)). Also, aromatic molecules such as phenol and 2-naphthol have been chosen to be comparnd to alchols in their co-adsorption with the DSS in order to have a better knowledge of the surface heterogeneity of the activated carbon. Then, the maximal adsoiption capacity (GAMMAtion. A 3 h contact time is required for the obtention of the equilibrium DSS adsorption; this stabilization in the rapid phase of the adsorption is more rapidly achieved in the presence of a co-adsorbate. The effect of the alcohols studied in the millimolar range: methanol, ethanol, propanol, butanol, pentanol at equilibrium time is shown in F'ig. 1 the dimensionless adsorbed concentration C/CO is unchanged for methanol and ethanol but diminished in the cther cases. The low solubility of pentanol in water seeems to be a limiting factor for this study; so that the dodecanol is solubilized in methanol before being adde.d to water solutions of DSS. The micromolar range of dodecanol is sufficient to strongly diminish DSS adsorption on activated carbon (Fig. 2). Kf evolttion is of the same order. The large steric hindrance and hydrophobic effects of the chain of dodecanol and its equally good adsorbability (Schwuger and Sa.olka, 1977) give competitive phenomena in the co-adsorption of the DSS. A compact molecule such as phenol or 2-naphthol is compared to these results (Figs 3 and 4). The sequence of the added co-adsorbates in the adsorption can modify the kinetic external mass transfer coefficient and also the pseudo equilibrium parametev . are important to obtain the CAG filter performance. The influence of Ca2+ ion:, which are very important for DSS fixation onto the negative charged surface ef the CAP (Mazet a] al., 1988), is also studied. The results of the adsorption of DSS in the presence of phenol, naphthol (N-2) are noted on Fig. 3. No phenol effect on DSS appeared. The N-2 presence somewhat diminishes the adsorption of DSS (Fig. 5) and desorbs the DSS when it is added after 3 h adsorption contact time (Fig. 6) but, Kf values are not modified ( Fig. 7). Ca2+ ions give, and maintain good ->romotion of the adsorption of DSS only if simultneously present withthe DSS (Figs 5 and 6). The complex D5S-Ca2+ seems to be necessary to have supplementary sites on the carbon surface. For N-2 adsorption in the presence of DSS (Figs 8, 9.tnd 10), an inhibition effect can be observed; Kf is also diminished and if the DSS-Ca2+ mixture is first adsorbed, a stronger inhibition of the adosorpti
Page 55: pit35a00
08/24/94 Page -49- Increase of the anion and proton permeability of Saccharomyces carlsbergensis plasmalemma by a- alcohols as a possible cause of its de-energization. By PETROV VV; OKOROKOV LA In English YEAST, "*(7990)*** . Vo1. 6, No. 4, pp. 311-318. CODEA': YESTE. [90:94898 TOXLINE] ABSTRACT> BIOSIS COPYRIGHT: BIOL ABS. The effect of n-alcohols on ATP- dependent generation of DELTApH and Em across the plasma membrane vesicles of the yeast Saccharomyces carlsbergensis was investigated. The alcohols weie shown to collapse DELTApH and Em in the order C2 < C3 < C4 < C5 Itoreq. C6 gtoreq. C7 > C8 > Cll, the dissipation of Em being more pronounced. Inhibition of the plasmalemma H+-ATPase was insinificant; at low alchol concentrations its activity even increased. The basic reason for the toxic effect of the alcohols on the yeast cells was suggested to be due to the increase in the anion and proton permeability of the plasma membrane. Mg2+ partially prevented the increase in the plasmalemma ion permeability by the alcohols investigated. The role of hydrophobicity and electronic factors in regulating alcohol inhibition of cytochrome P-450-mediated aniline hydroxylation. By SHUSTERMAN AJ; JOHNSON AS In English CHEM-BIOL INTERACT, ***(1990)** . Vol. 74, No. 1-2, pp. 63-78. CODEN: CBINA. [90:78373 TOXLINE] ABSTRACT> BIOSIS COPYRIGHT: BIOL ABS. The role of hvdrophobicity and electronic factors in regulating alcohol inhibition of cy[ochrome P- 450-mediated aniline p-hydroxylation has been investigated by the formulation of quantitative structure-activity relationships. The activity of linear primary alcohols and unhindered linear scondary alcohols shows a linear dependence on log P, where P is the octanol- water partition coefficient. Hindered primary and secondary alcohols are less active than this relationship predicts. An equation describing the activity of both hindered and unhindered primary and secondary alcohols shows that alcohol inhibition of aniline hydroxylation is regulated by hydrophobicity and steric effects. No role for electronic factors can be discerned. S.milarities are found between alcohol inhibition and the binding of alkyl amines to cytochrome P-450, suggesting that alcohols may bind to the amine binding :ite. (25 CD DEGRADATION OF ETHIDIUM BROMIDE IN ALCOHOLS . .p c0 By LUNN G; SANSONE EB In English w BIOTECHNIQUES, ***(1990)*** . Vo1. 8, No. 4, pp. 372-373. CODEN: u BTNQD. [90:70843 TOXLINE] ABSTRACT> BIOSIS COPYRIGHT: BIOL ABS. RRM MUTAGEN DISPOSAL HAZARDOUS WAS NITRITE HYPOPHOSPHOROUS ACID

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