Effects of chronic treatment with ethanol on the development of cross-tolerance to other alcohols and pentobarbital. 1992

A D Lê, and J M Khanna, and H Kalant
Department of Primary Mechanisms Research and Development, Addiction Research Foundation of Ontario, Toronto, Canada.

The development of cross-tolerance to various alcohols and pentobarbital was examined in ethanol (EtOH)-treated mice. Chronic EtOH treatment (dosage rising in steps from 3.5-4.5 g/kg i.p. daily during a 23-day period) produced tolerance to its hypnotic effect. Such tolerance was seen as a reduction in the duration of loss of righting reflex (LRR), as well as higher blood EtOH levels at the offset of LRR, in EtOH-treated mice as compared to saline-treated controls. Cross-tolerance was shown by shifts in dose-response curves for the LRR induced by n-propanol and t-butanol. Such treatment, however, did not confer functional cross-tolerance to n-butanol and pentobarbital. Because n-butanol and pentobarbital are more lipid-soluble, whereas EtOH, n-propanol and t-butanol have low degrees of lipid solubility, the development of cross-tolerance among these sedative-hypnotic drugs might be related to their relative degrees of lipid solubility.

UI MeSH Term Description Entries
D006993 Hypnotics and Sedatives Drugs used to induce drowsiness or sleep or to reduce psychological excitement or anxiety. Hypnotic,Sedative,Sedative and Hypnotic,Sedatives,Hypnotic Effect,Hypnotic Effects,Hypnotics,Sedative Effect,Sedative Effects,Sedatives and Hypnotics,Effect, Hypnotic,Effect, Sedative,Effects, Hypnotic,Effects, Sedative,Hypnotic and Sedative
D008297 Male Males
D010424 Pentobarbital A short-acting barbiturate that is effective as a sedative and hypnotic (but not as an anti-anxiety) agent and is usually given orally. It is prescribed more frequently for sleep induction than for sedation but, like similar agents, may lose its effectiveness by the second week of continued administration. (From AMA Drug Evaluations Annual, 1994, p236) Mebubarbital,Mebumal,Diabutal,Etaminal,Ethaminal,Nembutal,Pentobarbital Sodium,Pentobarbital, Monosodium Salt,Pentobarbitone,Sagatal,Monosodium Salt Pentobarbital
D012018 Reflex An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord.
D004361 Drug Tolerance Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from DRUG RESISTANCE wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from MAXIMUM TOLERATED DOSE and NO-OBSERVED-ADVERSE-EFFECT LEVEL. Drug Tolerances,Tolerance, Drug,Tolerances, Drug
D000431 Ethanol A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES. Alcohol, Ethyl,Absolute Alcohol,Grain Alcohol,Alcohol, Absolute,Alcohol, Grain,Ethyl Alcohol
D000433 1-Propanol A colorless liquid made by oxidation of aliphatic hydrocarbons that is used as a solvent and chemical intermediate. Alcohol, Propyl,Propanol,n-Propanol,Propyl Alcohol
D000440 Butanols Isomeric forms and derivatives of butanol (C4H9OH). Alcohols, Butyl,Butanol,Butylhydroxides,Hydroxybutanes,Butyl Alcohols
D000704 Analysis of Variance A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable. ANOVA,Analysis, Variance,Variance Analysis,Analyses, Variance,Variance Analyses
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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