Synthesis and pharmacological evaluation of phenolic 2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinolin-4-ols as a new norepinephrine potentiator. 1994

M Kihara, and M Ikeuchi, and Y Kobayashi, and Y Nagao, and M Hashizume, and H Moritoki
Faculty of Pharmaceutical Sciences, University of Tokushima, Japan.

2-Methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline-4-ol(PI-OH) (2a) and its derivatives form a new class of compounds possessing norepinephrine (NE) potentiating activity. As a new series of compounds, the isomeric 4-(4-hydroxyphenyl)- and 4-(3-hydroxyphenyl)-2-methyl-1,2,3,4- tetrahydroisoquinolin-4-ols (3a and 3b), and 4-(3,4-dihydroxyphenyl)-1,2,3,4-tetrahydroisoquinolin-4-ol (3c) were prepared and their NE potentiating activities were evaluated. The 4-(4-hydroxyphenyl) analogue (3a) had only moderate activity and the 4-(3-hydroxyphenyl) analogue (3b) possessed a slightly higher activity than PI-OH. The 4-(3,4-dihydroxyphenyl) analogue (3c) was the most active compound and the pD2 value was 7.71 +/- 0.06 (activity ratio; 26.9 fold) at a concentration of 3 x 10(-6) M. These results indicate the importance of dihydroxyphenylethanolamine moiety of 3c for the inhibition of NE uptake.

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)
D009119 Muscle Contraction A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. Inotropism,Muscular Contraction,Contraction, Muscle,Contraction, Muscular,Contractions, Muscle,Contractions, Muscular,Inotropisms,Muscle Contractions,Muscular Contractions
D009638 Norepinephrine Precursor of epinephrine that is secreted by the ADRENAL MEDULLA and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the LOCUS CERULEUS. It is also found in plants and is used pharmacologically as a sympathomimetic. Levarterenol,Levonorepinephrine,Noradrenaline,Arterenol,Levonor,Levophed,Levophed Bitartrate,Noradrenaline Bitartrate,Noradrénaline tartrate renaudin,Norepinephrin d-Tartrate (1:1),Norepinephrine Bitartrate,Norepinephrine Hydrochloride,Norepinephrine Hydrochloride, (+)-Isomer,Norepinephrine Hydrochloride, (+,-)-Isomer,Norepinephrine d-Tartrate (1:1),Norepinephrine l-Tartrate (1:1),Norepinephrine l-Tartrate (1:1), (+,-)-Isomer,Norepinephrine l-Tartrate (1:1), Monohydrate,Norepinephrine l-Tartrate (1:1), Monohydrate, (+)-Isomer,Norepinephrine l-Tartrate (1:2),Norepinephrine l-Tartrate, (+)-Isomer,Norepinephrine, (+)-Isomer,Norepinephrine, (+,-)-Isomer
D004298 Dopamine One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action. Hydroxytyramine,3,4-Dihydroxyphenethylamine,4-(2-Aminoethyl)-1,2-benzenediol,Dopamine Hydrochloride,Intropin,3,4 Dihydroxyphenethylamine,Hydrochloride, Dopamine
D004357 Drug Synergism The action of a drug in promoting or enhancing the effectiveness of another drug. Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
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
D014662 Vasoconstrictor Agents Drugs used to cause constriction of the blood vessels. Vasoactive Agonist,Vasoactive Agonists,Vasoconstrictor,Vasoconstrictor Agent,Vasoconstrictor Drug,Vasopressor Agent,Vasopressor Agents,Vasoconstrictor Drugs,Vasoconstrictors,Agent, Vasoconstrictor,Agent, Vasopressor,Agents, Vasoconstrictor,Agents, Vasopressor,Agonist, Vasoactive,Agonists, Vasoactive,Drug, Vasoconstrictor,Drugs, Vasoconstrictor
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D018482 Muscle, Skeletal A subtype of striated muscle, attached by TENDONS to the SKELETON. Skeletal muscles are innervated and their movement can be consciously controlled. They are also called voluntary muscles. Anterior Tibial Muscle,Gastrocnemius Muscle,Muscle, Voluntary,Plantaris Muscle,Skeletal Muscle,Soleus Muscle,Muscle, Anterior Tibial,Muscle, Gastrocnemius,Muscle, Plantaris,Muscle, Soleus,Muscles, Skeletal,Muscles, Voluntary,Skeletal Muscles,Tibial Muscle, Anterior,Voluntary Muscle,Voluntary Muscles
D066298 In Vitro Techniques Methods to study reactions or processes taking place in an artificial environment outside the living organism. In Vitro Test,In Vitro Testing,In Vitro Tests,In Vitro as Topic,In Vitro,In Vitro Technique,In Vitro Testings,Technique, In Vitro,Techniques, In Vitro,Test, In Vitro,Testing, In Vitro,Testings, In Vitro,Tests, In Vitro,Vitro Testing, In

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