Stereoselective interaction of tetrahydroisoquinolines in β-adrenoceptor systems

Michael T. Piascik, Peter Osei-Gyimah, Duane D. Miller, Dennis R. Feller

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


In selected β1- (heart, lipolysis) and β2-adrenoceptor (trachea) systems, the interaction of racemic-trimetoquinol (TMQ) and the erythro- and threo-diastereomers of 1-(3′,4′,5′-trimethoxy-α-hydroxybenzyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (α-hydroxy TMQ) was investigated. Each tetrahydroisoquinoline possessed agonist activity in these β-adrenoceptor systems. The rank order of potency observed for these compounds was racemic-TMQ > erythro-α-hydroxy TMQ > threo-α-hydroxy TMQ. Using isolated fat adipocytes, a favorable correlation was observed between the elevation in c-AMP and pharmacological response for the TMQ stereoisomers and diastereomers of α-hydroxy TMQ. The rise in intracellular c-AMP produced by (-)- and (+)-TMQ in fat cells was blocked by the presence of propranolol, and not in the presence of phentolamine. Since considerably higher concentrations (>10-4 M) of these compounds were required to produce a significant inhibition of c-AMP phosphodiesterase activity in adipose tissue, it is proposed that the lipolytic response is a result of stereoselective interaction of these tetrahydroisoquinolines at the level of membrane-bound adenylate cyclase.

Original languageEnglish
Pages (from-to)393-401
Number of pages9
JournalEuropean Journal of Pharmacology
Issue number4
StatePublished - Apr 15 1978

Bibliographical note

Funding Information:
This study was supported in part by a grant from the National Institutes of Health, USPHS (NS 10896). One of us (M.T.P.) is a Fellow of the American Foundation for Pharmaceutical Education. We also thank Dr. Popat Patil for his constructive comments in the design of these studies, and Mrs. Raji Ra-man for her technical assistance.


  • Diastereomers
  • Stereoisomers
  • Trimetoquinol
  • cAMP
  • α-Hydroxytrimetoquinol
  • β-Adrenoceptors

ASJC Scopus subject areas

  • Pharmacology


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