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Biomedical subjects

P Lundborg

Publications and source records attributed to P Lundborg.

At least 19 recordsLinked to original sources
PubMed1979

Haemodynamic effects and pharmacokinetics of a new selective beta1-adrenoceptor agonist, prenalterol, and its interaction with metoprolol in man.

The haemodynamic effects of the selective beta1-adrenoceptor agonist prenalterol were studied in healthy subjects before and after therapeutic doses of the selective beta1-adrenoceptor blocker metoprolol. Plasma levels of the drugs were also determined in order to calculate certain pharmacokinetic variables. Intravenous infusion of prenalterol 0.13, 0.25 and 0.50 mg induced a dose-dependent decrease in total electromechanical systole (QA2) and pre-ejection period (PEP). The effect on left ventricular ejection time (LVET) was not significant. Increases in systolic blood pressure and heart rate were dose-dependent. Diastolic blood pressure did not change significantly. When metoprolol had been administered in a cumulative dose of 150 mg (mean maximal plasma level, 284 nmol/l) prenalterol had to be administered in doses that were twelve times higher than before the beta-blocker in order to induce the same haemodynamic effects. Prenalterol was rapidly distributed with an average half life of 8 min. This indicates that distribution equilibrium will be achieved within 30 min after intravenous administration. The overall elimination rate in the post-distributive phase corresponded to an average half life of 2.0 h.

Adrenergic beta-Agonists↗
PubMed1979

Pharmacokinetics of metoclopramide intravenously and orally determined by liquid chromatography.

1 A rapid and sensitive method, based on liquid chromatography, has been developed for determination of metoclopramide concentrations in plasma and urine samples. Concentrations down to 15 nmol/1 (5 ng/ml) of plasma and 100 nmol/1 (30 ng/ml) of urine could be determined with a relative standard deviation of less than or equal to 10%. The method was used to study disposition of metoclopramide in healthy volunteers following single doses intravenously and orally as aqueous solution and a slow release tablet. 2 The initial distribution after intravenous administration was very rapid. The elimination half-life postdistribution was 4.9 h. The apparent volume of distribution, Vd, was 3.0 1/kg body weight. On average 19% was excreted unchanged after intravenous administration of 5 and 10 mg (15 and 30 mumol) of drug. The rate of absorption of metoclopramide was delayed after administration of a slow release tablet and the maximum plasma concentration was about 50% lower than after a solution. The extent of bioavailability was the same following the two different formulations suggesting a first-pass elimination of 25-40%.

Administration, Oral↗
PubMed1979

Bioavailability and disposition of metoprolol and hydrochlorothiazide combined in one tablet and of separate doses of hydrochlorothiazide.

1. The plasma levels and the urinary excretion of hydrochlorothiazide (HCT) have been studied after administration of single doses of 12.5 and 25 mg of the drug in solution and in combination with 100 mg of the selective beta 1-adrenoreceptor antagonist metoprolol in a rapidly dissolving tablet. 2. Metoprolol did not significantly influence the bioavailability or the time-course of HCT. 3. HCT had no significant effect on the time-course or the plasma levels of metoprolol. The average half-life, 4.4 +/- 0.9 h, is about the same as previously observed for separate doses of this drug. 4. It seems unlikely that repeated doses of the combination product studied will lead to biopharmaceutic or pharmacokinetic interactions of clinical importance.

Biological Availability↗
PubMed1979

The peripheral platelet count and the isoprenaline-induced splenic platelet pooling in response to beta-adrenoceptor blockade.

Previous reports have shown that a single, oral dose of 50 mg metoprolol (a selective beta-1-receptor antagonist) causes a significant increase in the peripheral platelet count by releasing platelets from the spleen. In the present study 20 healthy volunteers received 50 mg metoprolol and 40 mg propranolol orally. Both drugs induced a statistically significant increase in the platelet count lasting more than 5 h. In addition, the effect of metoprolol and propranolol on beta-adrenoceptor mediated splenic platelet trapping was studied on 7 healthy subjects who received intravenous infusions of isoprenaline before and after the ingestion of these 2 beta-blocking drugs. It was demonstrated that the isoprenaline mediated decrease in the venous platelet count was diminished by both propranolol and metoprolol but the former compound appeared to be more potent in this respect. We conclude that both selective and non-selective beta-receptor blockade causes an increase in the peripheral platelet concentration during rest as well as during beta-adrenoceptor stimulation.

Adrenergic beta-Antagonists↗
PubMed1979

Interaction studies between three antidepressant drugs (chlorimipramine, imipramine and zimelidine) and noradrenaline, tyramine and vagal stimulation on the heart rate and blood pressure in dogs.

Anaesthetized Beagle dogs were given increasing intravenous doses of imipramine, chlorimipramine or zimelidine. At each dose interval the interference of the drug administered with the effects on blood pressure and heart rate of vagal stimulation, NA injection and tyramine injection was investigated. Also, the in vitro uptake of 5-HT into platelets after in vivo administration to unanaesthetized dogs of 5 mg chlorimipramine or 5 mg zimelidine was studied. Chlorimipramine and zimelidine were found to be about equipotent as regards 5 HT-uptake into platelets after in vivo administration. Imipramine and chlorimipramine potentiated the effects of NA after the 2 mg/kg dose. Imipramine but not chlorimipramine interfered with the effects of tyramine after the 4 mg/kg dose. Zimelidine did not interfere with either NA or tyramine at any dose level studied (maximal cumulative dose 62 mg/kg). The effect of vagal stimulation was significantly inhibited after 8 mg/kg (cumulative dose 14 mg/kg) of imipramine and 16 mg/kg (cumulative dose 30 mg/kg) of chlorimipramine and zimelidine, respectively. It is concluded that zimelidine in comparison with imipramine and chlorimipramine has no or at most a slight effect on peripheral adrenergic neurones. It has less pronounced anticholinergic properties than imipramine but is about equipotent to chlorimipramine in this respect.

Allylamine↗
PubMed1979

Regional changes in monoamine synthesis in the developing rat brain during hypoxia.

4, 14 and 28 days old rats were exposed to hypoxic environment of 6% O2-94% N2 for 30 min. Tyrosine hydroxylase and tryptophan hydroxylase activity was studied in different brain regions (hemispheres, striatum, midbrain and brainstem in vivo by measuring the accumulation of dihydroxyphenylalanine (Dopa) and 5-hydroxytryptophan (5-HTP) respectively, after inhibition of aromatic L-amino acid decarobyxlase with NSD 1015. Tyrosine and tryptophan levels in the different brain regions were measured simultaneously. The tyrosine and tryptophan levels in the various brain parts were generally not influenced during exposure to hypoxia. Tyrosine hydroxylase activity decreased in most areas in the 4 and 14 days old rats, and all brain areas studied in the 28 days old rats. Tryptophan hydroxylase activity decreased markedly in all brain areas at all ages studied. It is concluded that the enzymes tyrosine hydroxylase as well as tryptophan hydroxylase seem to be equally affected during hypoxia in the different brain regions studied.

5-Hydroxytryptophan↗
PubMed1978

The peripheral platelet count in response to adrenergic alpha-and beta-1-receptor stimulation.

The aim of the present work was to investigate the effect of adrenergic alpha- and beta-1-receptor stimulation on the peripheral platelet count. The experiments were carried out on 8 healthy male volunteers using radioisotopically labelled platelets. 3 subjects received i.v. infusions of adrenaline (0.09 microgram X kg-1 X min-1) before and after the ingestion of 40 mg propranolol. In response to the first infusion there was an instant increase in the venous platelet-bound radioactivity (PBR) which amounted to 12% over basal value. This effect of adrenaline seemed to be potentiated by propranolol pretreatment. 5 subjects received i.v. infusions of the highly selective beta-1-receptor agonist H 133/22 (prenalterol, Hässle, Sweden). In response to a cumulative dose of 4.75 mg prenalterol a slight but significant (P less than 0.05) decrease in PBR occurred. It is concluded that alpha-receptor stimulation causes a depletion of platelets from the exchangeable splenic platelet pool resulting in a concomitant increase in the peripheral platelet count. Beta-receptor stimulation has an opposite effect on the spleen. The trapping of platelets by the spleen is mediated both via beta-1- and beta-2-receptors, but the effect of beta-2-receptor stimulation seems to predominate.

Adrenergic beta-Agonists↗
PubMed1978

Effect of hypoxia on monoamine synthesis in brains of developing rats. III. Various O2 levels.

1-, 4-, 14- and 28-day-old rats were exposed to a hypoxic environment of 5.9, 8.0 or 12.0% O2 during a period of 30 min. In the brain, tyrosine hydroxylase and tryptophan hydroxylase activity was studied in vivo by measuring the accumulation of dihydroxyphenylalanine (DOPA) and 5-hydroxytryptophan (5-HTP), respectively, after inhibition of L-aromatic amino acid decarboxylase with NSD 1015. Tyrosine and tryptophan levels in the brain were measured simultaneously. The brain tyrosine and tryptophan levels were generally not influenced either by age or hypoxic levels. Tyrosine and tryptophan hydroxylase activity decreased to about the same extent during the various hypoxic levels at all ages studied. It is concluded that the first, rate-limiting, step in the synthesis of the monoamine neurotransmittors dopamine (DA), noradrenaline (NA) and 5-hydroxy-tryptophan (5-HT) is affected during moderate as well as severe hypoxia at all stages of development.

5-Hydroxytryptophan↗
PubMed1978

Effects of terbutaline on the pressure volume relationship in fetal rabbit lung.

The pressure-volume relationship in preterm rabbit lung was studied at 28 days of gestation. Injection of 0.1 mg terbutaline, a selective beta2-receptor stimulating drug, significantly increased the volume of air at equivalent low transpulmonary pressures, compared to a saline treated group and an untreated group. These findings indicate an increased pulmonary distensibility of the fetal rabbit lung after terbutaline administration. The mechanism of action is discussed and surfactant mediated effects are suggested to be the probable explanation.

Animals↗
PubMed1977

The relation between baseline and 150 min platelet counts in response to selective beta-1-receptor blockade. An experimental study on healthy subjects.

In 30 healthy volunteers after an oral administration of 50 mg metoprolol basal and 150 min platelet counts were determined. A significant negative correlation (p less than 0.01) between the baseline platelet count and the percentage increase at 150 min was shown to be present. It is postulated that this observation reflects interindividual differences between the magnitude of the exchangeable splenic platelet pool.

Administration, Oral↗