Antagonism of ethanol intoxication in rats by inhibitors of phenylethanolamine N-methyltransferase. 1990

I N Mefford, and R G Lister, and M Ota, and M Linnoila
Section on Clinical Pharmacology, National Institute of Mental Health, Bethesda, Maryland 20892.

The probable involvement of brain epinephrine in the expression of the acute sedative and intoxicating effects of ethanol and pentobarbital is demonstrated. Two selective inhibitors of phenylethanolamine N-methyltransferase (PNMT), LY134046 and LY78335, proved to be potent and long-lasting antagonists of ethanol intoxication in rats. Acute antagonism of pentobarbital-induced intoxication was observed with LY134046. The present results are compatible with a role for central epinephrine synthesis in ethanol and pentobarbital-induced sedation and intoxication in rats.

UI MeSH Term Description Entries
D007546 Isoquinolines A group of compounds with the heterocyclic ring structure of benzo(c)pyridine. The ring structure is characteristic of the group of opium alkaloids such as papaverine. (From Stedman, 25th ed)
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
D010625 Phenylethanolamine N-Methyltransferase A methyltransferase that catalyzes the reaction of S-adenosyl-L-methionine and phenylethanolamine to yield S-adenosyl-L-homocysteine and N-methylphenylethanolamine. It can act on various phenylethanolamines and converts norepinephrine into epinephrine. (From Enzyme Nomenclature, 1992) EC 2.1.1.28. Phenethanolamine N-Methyltransferase,Noradrenalin N-Methyltransferase,Noradrenaline N-Methyltransferase,Norepinephrine Methyltransferase,Norepinephrine N-Methyltransferase,Methyltransferase, Norepinephrine,Noradrenalin N Methyltransferase,Noradrenaline N Methyltransferase,Norepinephrine N Methyltransferase,Phenethanolamine N Methyltransferase,Phenylethanolamine N Methyltransferase
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D003975 Diazepam A benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnesic properties and a long duration of action. Its actions are mediated by enhancement of GAMMA-AMINOBUTYRIC ACID activity. 7-Chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one,Apaurin,Diazemuls,Faustan,Relanium,Seduxen,Sibazon,Stesolid,Valium
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
D001552 Benzazepines Compounds with BENZENE fused to AZEPINES.
D001596 Benzylamines Toluenes in which one hydrogen of the methyl group is substituted by an amino group. Permitted are any substituents on the benzene ring or the amino group. Phenylmethylamine,alpha-Aminotoluene,alpha Aminotoluene

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