Carazolol, an extremely potent β-adrenergic blocker: Binding to β-receptors in brain membranes

Robert B. Innis, Fernando M A Corrêa, Solomon H Snyder

Research output: Contribution to journalArticle

Abstract

The binding of (±)-[3H]carazolol, a recently developed β-adrenergic antagonist of high potency, to rat cerebral cortical membranes is compared to the binding of (-)-[3H]dihydroalprenolol (3H-DHA). 3H-Carazolol binds saturably to cortical β-receptors with a KD of 0.15 nM, a value approximately four times lower than that for 3H-DHA. Considering that 3H-carazolol was used as the racemic mixture and 3H-DHA as the (-)-isomer, an equivalent formulation of 3H-carazolol would be 8-10 times more potent than 3H-DHA. This increased affinity can be explained by the observed two fold greater association rate constant and a two fold lower dissociation rate constant. The drug displacement profile of 3H-carazolol binding is very similar to that of 3H-DHA. 3H-Carazolol has equal displacements constants when binding is performed in calf cerebral cortex (which contains mainly β1 receptors) and calf cerebellum (which contains mainly β2 receptors), indicating that 3H-carazolol binds with equal affinity to β1 and β2 receptors. The percent free drug (i.e. unbound to serum proteins) for both carazolol and propranolol in rabbit serum is approximately 10%. At physiologically equivalent doses of carazolol and propranolol in the rabbit, there is no detectable free β-blocking activity at 15, 30 or 60 min after intravenous injection of carazolol, although substantial propranolol activity is detected.

Original languageEnglish (US)
Pages (from-to)2255-2264
Number of pages10
JournalLife Sciences
Volume24
Issue number24
DOIs
StatePublished - Jun 11 1979

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Adrenergic Antagonists
Brain
Dihydroalprenolol
Membranes
Propranolol
Rate constants
carazolol
Rabbits
Intravenous Injections
Isomers
Pharmaceutical Preparations
Cerebral Cortex
Cerebellum
Rats
Blood Proteins
Association reactions

ASJC Scopus subject areas

  • Pharmacology

Cite this

Carazolol, an extremely potent β-adrenergic blocker : Binding to β-receptors in brain membranes. / Innis, Robert B.; Corrêa, Fernando M A; Snyder, Solomon H.

In: Life Sciences, Vol. 24, No. 24, 11.06.1979, p. 2255-2264.

Research output: Contribution to journalArticle

Innis, Robert B. ; Corrêa, Fernando M A ; Snyder, Solomon H. / Carazolol, an extremely potent β-adrenergic blocker : Binding to β-receptors in brain membranes. In: Life Sciences. 1979 ; Vol. 24, No. 24. pp. 2255-2264.
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