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Neuropharmacology. 1986 Jan;25(1):21-4.
The beta 2-adrenoceptor agonists clenbuterol and salbutamol enhance the hypothermic action of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) in mice by a central mechanism.

Green AR, Goodwin GM, De Souza RJ, Heal DJ.

The hypothermic response of mice to injection of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was enhanced by injection of the beta 2-adrenoceptor agonist clenbuterol with an ED50 of 0.4 mg/kg. This effect of clenbuterol is through a central mechanism since salbutamol, a beta 2-adrenoceptor agonist with poor penetration into the brain, had no effect at a dose of 2 mg/kg, whereas intracerebroventricular injection of clenbuterol (3 micrograms) or salbutamol (2 micrograms), produced a significant enhancement. The enhancing effect of clenbuterol was unaffected by pretreatment with the beta 1-adrenoceptor antagonist metoprolol but was totally antagonised by the beta 2-adrenoceptor antagonist ICI 118,551 and to a lesser extent by butoxamine. Clenbuterol therefore enhances the function of the presynaptic 5-HT1 receptor through a beta 2-adrenoceptor mechanism.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2936976&dopt=Abstract




Atherosclerosis. 1988 Aug;72(2-3):163-72.
Atherosclerosis in rabbits identified as high and low responders to an atherogenic diet and the effect of treatment with a beta 1-blocker.

Lindqvist P, Olsson G, Nordborg C, Bondjers G, Brautigam J, Ostlund-Lindqvist AM.

Department of Medical and Physiological Chemistry, University of Uppsala, Sweden.

In order to investigate whether initial plasma lipid concentrations could be used to distinguish between high and low responders to an atherogenic diet, rabbits were divided into 3 groups according to their plasma concentrations of cholesterol and phospholipids after 4 weeks on a standard rabbit diet. Plasma cholesterol and phospholipid levels were less than 0.5 mM, less than 1.1 mM, respectively, in group 1 (n = 17), greater than 0.5 mM, less than 1.1 mM, in group 2 (n = 13), and greater than 0.5 mM, greater than or equal to 1.1 mM, in group 3 (n = 14). After 7 weeks on a diet containing 0.25% cholesterol and 3% coconut oil, animals in groups 1 and 2 had a lower increase in their plasma lipid levels compared with group 3. Half of each group was then treated with the beta 1-adrenoceptor antagonist metoprolol during the next 14 weeks on the atherogenic diet. At the end of the study, the extent of atherosclerosis both in the aortas and in the coronary arteries of the control animals showed a positive correlation to plasma cholesterol and to plasma phospholipid concentrations integrated over time. The metoprolol-treated animals in groups 1 and 2 had a reduction of atherosclerosis compared with their respective controls. We conclude that subpopulations of rabbits that react differently on an atherogenic diet can be identified by their initial plasma lipid levels, and that metoprolol treatment of low responders to an atherogenic diet significantly reduces atherosclerotic lesions of the aorta.

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J Pharmacol Exp Ther. 1994 Nov;271(2):860-7.
Metabolic disposition of imipramine in oriental subjects: relation to metoprolol alpha-hydroxylation and S-mephenytoin 4'-hydroxylation phenotypes.

Koyama E, Sohn DR, Shin SG, Chiba K, Shin JG, Kim YH, Echizen H, Ishizaki T.

Department of Clinical Pharmacology, International Medical Center of Japan, Tokyo.

We studied the metabolic disposition of imipramine by measuring imipramine and its metabolites in plasma and urine simultaneously after a single oral dose of 25 mg of imipramine hydrochloride administered to 16 healthy (three Japanese and 13 Korean) volunteers. Four of the subjects were poor metabolizers (PMs) of metoprolol but extensive metabolizers (EMs) of S-mephenytoin (PMML/EMMP), five subjects were EMs of metoprolol but PMs of S-mephenytoin (EMML/PMMP) and seven subjects were EMs of both metoprolol and S-mephenytoin (EMML/EMMP). The mean (+/- S.D.) oral clearances of imipramine were smaller in the PMML/EMMP group and the EMML/PMMP group than in the EMML/EMMP group, although a statistical difference (P < .05) was found only in the EMML/PMMP vs. the EMML/EMMP group. The mean area under the plasma concentration-time curve (AUC) of desipramine was 9 times greater (P < .01) in PMML/EMMP group, whereas the mean value was 0.6 times smaller (P < .05) in the EMML/PMMP group than in the EMML/EMMP group. The log10 metoprolol/alpha-hydroxymetoprolol ratio correlated positively with the AUC of desipramine (P < .01) and with the AUC ratio of desipramine/imipramine (P < .05) but negatively with the AUC ratio of 2-hydroxyimipramine/imipramine (P < .05). Log10 percent 4'-hydroxymephenytoin excreted in 8-hr urine correlated positively with the AUC of desipramine (P < .01) and with the AUC ratio of desipramine/imipramine (P < .01). The urinary excretions of imipramine and its metabolites also reflected the data derived from plasma samples in the three different phenotype-paired panels.(ABSTRACT TRUNCATED AT 250 WORDS)

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7965806&dopt=Abstract












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