Stereoselective interaction of tetrahydroisoquinolines in β-adrenoceptor systems

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

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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 (US)
Pages (from-to)393-401
Number of pages9
JournalEuropean Journal of Pharmacology
Volume48
Issue number4
DOIs
StatePublished - Apr 15 1978
Externally publishedYes

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Tretoquinol
Tetrahydroisoquinolines
Adrenergic Receptors
Adenosine Monophosphate
Adipocytes
Stereoisomerism
Phentolamine
Lipolysis
Phosphoric Diester Hydrolases
Trachea
Adenylyl Cyclases
Propranolol
Adipose Tissue
Fats
Pharmacology

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Stereoselective interaction of tetrahydroisoquinolines in β-adrenoceptor systems. / Piascik, Michael T.; Osei-Gyimah, Peter; Miller, Duane; Feller, Dennis R.

In: European Journal of Pharmacology, Vol. 48, No. 4, 15.04.1978, p. 393-401.

Research output: Contribution to journalArticle

Piascik, Michael T. ; Osei-Gyimah, Peter ; Miller, Duane ; Feller, Dennis R. / Stereoselective interaction of tetrahydroisoquinolines in β-adrenoceptor systems. In: European Journal of Pharmacology. 1978 ; Vol. 48, No. 4. pp. 393-401.
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