title: Receptor occupancy in lumbar CSF as a measure of the antagonist activity of atenolol, metoprolol and propranolol in the CNS.
abstract: 1. The antagonist activity of atenolol, metoprolol and propranolol in the CNS was estimated by determining the extent to which the drugs occupy animal beta 1- and beta 2-receptors in CSF ex vivo at the time of lumbar puncture. 2. Five CSF and plasma samples were obtained 4 h after drug intake from subjects treated for hypertension with atenolol, 100 mg once daily and five from subjects treated with metoprolol, 50 mg three times daily. Twenty-four samples were obtained 1, 2, 4 or 12 h after drug intake from subjects receiving a single 40 mg dose of propranolol. 3. The receptor occupancy in the samples was determined by adding beta 1-receptors of rabbit lung and beta 2-receptors of rat reticulocytes into the samples and labeling the receptors with a nonselective beta-adrenoceptor antagonist, (-)-[3H]-CGP-12177. 4. Atenolol and metoprolol occupied, as expected, larger fractions of beta 1- than beta 2-receptors in CSF and plasma samples. The receptor fraction occupied by atenolol in CSF was significantly (P < 0.05) lower than that occupied by metoprolol. The differences in occupancy between the drugs in plasma, however, were not statistically significant. 5. Propranolol occupied larger fractions of beta 2- than beta 1-receptors in the samples. Although propranolol concentrations in CSF were only 1/20-1/40 of those in plasma, the receptor occupancy of propranolol in CSF was similar to that in plasma.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Clinical Pharmacology, University of Turku, Finland.
authors.forename: T
authors.initials: T
authors.lastname: Kaila
authors.forename: R
authors.initials: R
authors.lastname: Marttila
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000134:cerebrospinal fluid* / Q000494:pharmacology; D000328:Adult; D000818:Animals; D001262:Atenolol / Q000134:cerebrospinal fluid / Q000494:pharmacology; D002490:Central Nervous System / Q000187:drug effects*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008790:Metoprolol / Q000134:cerebrospinal fluid / Q000494:pharmacology; D008875:Middle Aged; D011412:Propanolamines / Q000494:pharmacology; D011433:Propranolol / Q000134:cerebrospinal fluid / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*
chemical_list: D000317:Adrenergic alpha-Antagonists; D011412:Propanolamines; D011942:Receptors, Adrenergic, alpha; D001262:Atenolol; D011433:Propranolol; D008790:Metoprolol; C033394:CGP 12177