Pharmacodynamic response to Ro15-4513 in ethanol intoxicated dogs. 1996

D Whitmire, and L M Cornelius, and P S Whitmire
Biological Engineering Center, Driftmier Engineering Center, Athens, GA 30602-4435, USA.

The interaction of Ro15-4513 (5 mg/kg) with ethanol (3 g/kg, 60%w/v bolus) in dogs was investigated. Ro15-4513 challenge 120 minutes after a single ethanol dose had no significant effect on blood ethanol concentration or heart rate. In the same experiment, (1) blood acetaldehyde concentration was elevated to more than double the control value (vehicle only, no Ro15-4513), and (2) systolic blood pressure decreased to less than 60% of control. Further investigation revealed: (1) after Ro15-4513, area under the blood acetaldehyde vs time curve was more than twofold greater (p = 0.0006) than control, and the area under the systolic blood pressure vs time curve was 76% (p = 0.0027) of control. Based on these results, we propose that an inter-relationship exists between Ro15-4513, blood acetaldehyde concentration, and systolic blood pressure in ethanol intoxicated dogs.

UI MeSH Term Description Entries
D008658 Inactivation, Metabolic Reduction of pharmacologic activity or toxicity of a drug or other foreign substance by a living system, usually by enzymatic action. It includes those metabolic transformations that make the substance more soluble for faster renal excretion. Detoxication, Drug, Metabolic,Drug Detoxication, Metabolic,Metabolic Detoxication, Drug,Detoxification, Drug, Metabolic,Metabolic Detoxification, Drug,Metabolic Drug Inactivation,Detoxication, Drug Metabolic,Detoxication, Metabolic Drug,Detoxification, Drug Metabolic,Drug Inactivation, Metabolic,Drug Metabolic Detoxication,Drug Metabolic Detoxification,Inactivation, Metabolic Drug,Metabolic Drug Detoxication,Metabolic Inactivation
D001794 Blood Pressure PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS. Systolic Pressure,Diastolic Pressure,Pulse Pressure,Pressure, Blood,Pressure, Diastolic,Pressure, Pulse,Pressure, Systolic,Pressures, Systolic
D002492 Central Nervous System Depressants A very loosely defined group of drugs that tend to reduce the activity of the central nervous system. The major groups included here are ethyl alcohol, anesthetics, hypnotics and sedatives, narcotics, and tranquilizing agents (antipsychotics and antianxiety agents). CNS Depressants,Depressants, CNS
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D006339 Heart Rate The number of times the HEART VENTRICLES contract per unit of time, usually per minute. Cardiac Rate,Chronotropism, Cardiac,Heart Rate Control,Heartbeat,Pulse Rate,Cardiac Chronotropy,Cardiac Chronotropism,Cardiac Rates,Chronotropy, Cardiac,Control, Heart Rate,Heart Rates,Heartbeats,Pulse Rates,Rate Control, Heart,Rate, Cardiac,Rate, Heart,Rate, Pulse
D000079 Acetaldehyde A colorless, flammable liquid used in the manufacture of acetic acid, perfumes, and flavors. It is also an intermediate in the metabolism of alcohol. It has a general narcotic action and also causes irritation of mucous membranes. Large doses may cause death from respiratory paralysis. Ethanal
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
D000435 Alcoholic Intoxication An acute brain syndrome which results from the excessive ingestion of ETHANOL or ALCOHOLIC BEVERAGES. Drunkenness,Intoxication, Alcoholic,Drunkennesses
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
D001386 Azides Organic or inorganic compounds that contain the -N3 group. Azide

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