Syntheses of conformationally defined analogues of tyramine and phenylethanolamine and their biological evaluations at central dopamine receptors and the active site of phenylethanolamine N-methyltransferase

Thesis/Dissertation · Thu Dec 31 23:00:00 EST 1987

OSTI ID:7246121

Ye, Q

Tyramine analogues 31-33 and 37-39 were evaluated for dopaminergic activities on rat striatal tissues with radioligands ({sup 3}H)SCH23390 for D-1 receptor and ({sup 3}H)spiroperidol for D-2 receptor. The tertiary amines 37-39 were generally more potent than the primary amines 31-33. In the primary amines, 33 (2-OH) was more potent than 31 and 32, and in the tertiary amines, 37 (4-OH) was more potent than 38 and 39 at both D-1 and D-2 receptors. The reduced activity of 31-33 and 37-39 compared with corresponding hydroxyl-substituted 2ATs is consistent with a negative interaction from the extra ethano bridge in their binding to the dopamine receptors. No selectivity was observed in both these conformationally defined tyramines (31-33 and 37-39) and conformationally restricted tyramines; a good correlation was observed between log IC{sub 5}O values at D-1 and D-2 receptors. The tyramines 31-33, the phenylethanolamines 45 and 46, and the phenylethylamine 44 (X, Y = H) were evaluated for activities as either substrates or inhibitors of phenylethanolamine N-methyltransferase (PNMT) by an in vitro radiochemical assay.

• Research Organization: Kansas Univ., Lawrence, KS (USA)
• OSTI ID: 7246121
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINES
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOCHEMICAL REACTION KINETICS
CARDIOTONICS
CARDIOVASCULAR AGENTS
CHEMICAL PREPARATION
DOPAMINE
DRUGS
ENZYME ACTIVITY
ENZYMES
HYDROGEN COMPOUNDS
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
KINETICS
LIGANDS
MEMBRANE PROTEINS
MOLECULAR STRUCTURE
NEUROREGULATORS
ORGANIC COMPOUNDS
PHENOLS
POLYPHENOLS
PROTEINS
RADIOASSAY
REACTION KINETICS
RECEPTORS
SYMPATHOMIMETICS
SYNTHESIS
TRACER TECHNIQUES
TRANSFERASES
TRITIUM COMPOUNDS
TYRAMINE