Phosphodiesterase inhibition and lipolytic action of the stereoisomers of trimetoquinol.
The isomers and racemate of trimetoquinol [TMQ; 6-7-dihydroxy-1-(3',4',5'-trimethoxybenzyl)-1,2,3,4-tetrahydroisoquinoline] as well as N-(3',4',5'-trimethoxyphenethyl)dopamine were all shown to be effective at promoting glycerol release from rat epididymal fat tissue. The rank order of potency observed for these compounds was (-)-TMQ greater than or equal to (+/-)-TMQ greater than greater than (+)-TMQ = N-(3',4',5-trimethoxyphenethyl)dopamine. (+/-)-TMQ and (-)-TMQ were the only agents capable of producing a maximal lipolytic response. None of the compounds tested were able to exhibit significant c-AMP phosphodiesterase inhibition. This study is the first report which shows that the beta-adrenoceptor activity of the isomers of TMQ does not correlate with an inhibition of c-AMP phosphodiesterase. An alternate mechanism of action for these compounds is proposed.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D000818:Animals; D002395:Catecholamines; D000242:Cyclic AMP / Q000378:metabolism; D004298:Dopamine / Q000031:analogs & derivatives / Q000378:metabolism; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology*; D007700:Kinetics; D050356:Lipid Metabolism; D008297:Male; D010726:Phosphodiesterase Inhibitors; D051381:Rats; D013237:Stereoisomerism; D014213:Tretoquinol / Q000494:pharmacology*
D002395:Catecholamines; D007546:Isoquinolines; D010726:Phosphodiesterase Inhibitors; C012081:N-(3',4',5'-trimethoxyphenethyl)dopamine; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D014213:Tretoquinol; D004298:Dopamine