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Biomedical subjects

P Lundborg

Publications and source records attributed to P Lundborg.

At least 73 records · Page 4Linked to original sources
PubMed1982

Survival of neonatal rats during hypoxia after monoamine stimulating agents.

Survival of 4 days old rats exposed to 6% O2-94% N2 was studied. Administration of L-DOPA (100 mg/kg) or L-5-HTP (100 mg/kg) reduced survival during hypoxia to about 30% of controls. A further reduction of survival time was noted after combined administration of L-DOPA and L-5-HTP. Administration of increasing doses of L-DOPA or L-5-HTP resulted in a dose-related decrease in neonatal survival time. After inhibition of the peripheral L-aminoacid decarboxylase with MK-486, L-DOPA caused the same reduction of survival time during hypoxia as after L-DOPA alone. Clonidine (2 mg/kg) was found to reduce hypoxic survival time to about 60%, while apomorphine had no effect compared to controls. Clonidine and apomorphine together had the same effect as clonidine alone. It is suggested that central monoamine neurotransmitters are involved in the mechanisms determining survival during neonatal oxygen deprivation.

5-Hydroxytryptophan↗
PubMed1981

Pharmacokinetic studies in man of the selective beta 1-adrenoceptor agonist, prenalterol.

The pharmacokinetics of prenalterol, a selective beta 1-adrenoceptor agonist, has been studied in healthy subjects, by following the plasma concentration and urinary excretion of the unchanged compound and its total radioactive metabolites after oral and intravenous administration. Each of six healthy subjects received a single i.v. dose (2.5 mg) and three oral doses (2.5, 5.0 and 10 mg) of prenalterol. The oral dose was administered as a solution. Three of the subjects received the intravenous and oral doses of 2.5 mg as tritiated drug. Prenalterol was rapidly and completely absorbed after oral administration. The peak plasma concentration was attained after about 0.5 h. About 25% of prenalterol reached the systemic circulation. Prenalterol was extensively distributed to extravascular tissues with a half-life of the distribution phase close to 7 min. About 90% of the dose was excreted in urine within 24 h irrespective of the route of administration, indicating complete absorption of the drug. On average 60% of the i.v. and 13% of the oral doses were excreted as unchanged drug. The elimination half-life of the compound was 1.8 h, and the decline in the plasma concentration of the metabolites indicated a slower elimination rate than for the unchanged drug. Dose-dependent kinetics were not observed after the oral doses examined.

Administration, Oral↗
PubMed1981

Effect of beta-adrenoceptor blockade on exercise performance and metabolism.

1. Carbohydrate and lipid metabolism and the capacity to perform prolonged submaximal physical exercise were studied in six young healthy subjects treated in a randomized double-blind fashion for 2 days with either placebo, the non-selective beta-adrenoceptor antagonist propranolol (80 mg b.i.d.) or the cardioselective agent metoprolol (100 mg b.i.d.). On day 3, 1 h after the last dose, the subjects exercised for 30 min periods followed up 10 min rest up to the point of exhaustion. 2. The capacity to perform exercise was decreased with both beta-adrenoceptor antagonists. However, at an equal degree of beta 1-adrenoceptor blockade, all subjects could exercise for a longer period of time on the cardioselective agent as compared with the non-selective drug. 3. Blood glucose levels decreased during exercise irrespective of the type of treatment, but the attenuation occurred most rapidly on propranolol. At exhaustion the average non-esterified fatty acid levels had increased 256% on placebo, 148% on metoprolol and 65% on propranolol. A significant positive correlation was found between changes in non-esterified fatty acid levels during exercise and total working time. It is concluded that beta-adrenoceptor blockade diminishes the capacity for prolonged sub-maximal exercise at least in part by reducing the availability of substrates to the working muscles.

Adult↗
PubMed1981

Neurochemical characteristics of cerebral catecholamine neurons during the postnatal development in the rat.

The development of cerebral dopamine (DA) and noradrenaline (NA) neurons was studied biochemically in 1- to 28-day-old rats. The precursor amino acid tyrosine increased to a steady state level in the whole brain during early postnatal age. After 14 days, however, there was a marked drop in the brain tyrosine level. In general, regional tyrosine levels also decreased between 4 and 28 days. DOPA accumulation was measured in whole brain and regional brain areas after inhibition of L-aromatic amino acid decarboxylase with NSD 1015. This is a well recognized method for estimating the in vivo rate of tyrosine hydroxylase activity. Whole brain DOPA accumulation after NSD 1015 increased progressively during postnatal life, and between 1 and 28 days a more than 3-fold increase was noted. Similar increases were also found in whole brain DA and NA levels during the corresponding period. Regional DA and NA levels generally increased with advancing age, with the highest DA levels in the striatum region and NA levels in the midbrain region. Regional DOPA accumulation after NSD 1015, reflecting in vivo tyrosine hydroxylase activity, increased in a similar fashion as the endogenous neurotransmitter levels. Measurements of DA and NA disappearance after alpha-methyltyrosine indicated the existence of an adult-like nerve impulse activity in DA neurons in the striatum and midbrain regions and in NA neurons in the hemispheres region of the 4-day-old rats. Gammahydroxybutyric acid (GHBA), which causes an inhibition of nerve impulse activity, was given to 4- and 28-day-old rats. This induced an initial increase in CA synthesis as measured by the NSD 1015 method at both ages. The results from this investigation show that the age-related regional increases in endogenous DA and NA levels closely follow the increase in regional tyrosine hydroxylase activity measured in vivo. Furthermore, the study also supports the view that feed-back mechanisms, resulting in an increased transmitter synthesis, exist in DA neurons after nerve impulse inhibition by GHBA at an early postnatal age.

Age Factors↗
PubMed1980

Metabolic and haemodynamic effects and pharmacokinetics of a new selective beta 1-adrenoceptor agonist, prenalterol, in man.

The metabolic and haemodynamic effects of three intravenous doses (0.5, 1.0 and 4.0 mg) of prenalterol, a selective beta 1-adrenoceptor agonist, were studied in 10 healthy male subjects. Plasma levels of prenalterol during the experiments were related to the haemodynamic effects. Prenalterol induced a dose-dependent increase in systolic blood pressure and heart rate. The maximal effects amounted to about 30 mm Hg and 15 beats/min, respectively, after the highest dose (4.0 mg). The diastolic blood pressure fell by a maximum of about 15 mm Hg. The effect of prenalterol on systolic blood pressure and heart rate persisted for about 3 h after the end of the last infusion, whereas that on diastolic blood pressure only lasted for 60 min. Compared with placebo, there was a moderate increase in plasma FFA and glycerol. A small rise in insulin level was also recorded, but no significant change was seen in other metabolic variables--triglycerides, glucose, lactate pyruvate. Serum potassium tended to decrease and serum sodium was unchanged. The initial distribution of prenalterol was rapid (half-life 7 min) and the overall elimination rate corresponded to a plasma half-life of 2 h. A linear relationship was found between the plasma level of prenalterol and its effects on systolic blood pressure and heart rate.

Adrenergic beta-Agonists↗
PubMed1980

Serotoninergic development in the postnatal rat brain.

Various characteristics of the developing serotoninergic system in the brain of rats aged 1 to 28 days were studied biochemically. The levels of the precursor amino acid tryptophan showed a maximal increase in the blood, brain and cerebrospinal fluid (CSF) during the 7th and 10th postnatal days. The development of tryptophan hydroxlyase activity measured in vivo by means of 5-hydroxytryptophan (5-HTP) accumulation after NSD 1015 was closely related to the 5-hydroxytryptamine (5-HT) levels at the various ages. 5-HTP accumulation and 5-HT levels increased most markedly after the second postnatal week. 5-Hydroxyindoleacetic acid (5-HIAA) levels were found to increase rapidly in the brain but somewhat more slowly in the CSF during the second week of postnatal development. Regional studies of 5-HTP accumulation after NSD 1015, 5-HT and 5-HIAA levels indicated a caudal to rostral way of maturation. The disappearance of 5-HT was measured after inhibition of tryptophan hydroxylase with H 22/54. The half-life generally decreased in the various brain parts with advancing age, and in the younger animals the shortest half-life was found in the most caudal brain parts. At 28 days of age the half-life was similar in all brain parts studied. These results indicate the existence of an adult like nerve impulse flow in the 5-HT neurons in the brain stem region of the newborn rats. The results from this investigation clearly indicate that th maturation of the different biochemical parameters of the 5-HT pathways develop in a caudal to rostral direction. The study also supports the view that tryptophan hydroxylase may be the limiting step in the development of the serotoninergic system.

5-Hydroxytryptophan↗
PubMed1980

Catecholamine concentration in the developing rat brain after gamma-hydroxybutyric acid.

The effect of the GABA receptor agonist gamma-hydroxybutyric acid (GHBA) on brain catecholamine concentration was investigated in 1 to 28 day old rats. The infant rats were given GHBA in various doses (375--1500 mg/kg) and the effects on whole brain or regional brain concentration of dopamine (DA) and noradrenaline (NA) were measured. Brain DA concentration increased in a dose-dependent way already from two days of postnatal age. In the regional brain study of the 14- and 28-day-old animals the increase in DA concentration was found to be almost exclusively located in the striatal region. Generally, no changes in NA concentration were found in the whole brain or various brain regions at any of the ages after GHBA. It is concluded that the inhibitory striatal-nigral neurons, utilizing GABA as a transmitter, are functionally developed during early postnatal age.

Aging↗
PubMed1980

Serotonin metabolism in neonatal rat brain during asphyxia and recovery.

Neonatal rats were exposed to 20 or 30 min of total or partial oxygen deprivation. During asphyxia and subsequent recovery the endogenous levels of tryptophan and 5-hydroxytryptamine (5-HT, serotonin) were measured. The activity of tryptophan hydroxylase, the first and rate limiting enzyme in the 5-HT synthesis pathway, was studied in vivo by measuring the accumulation of 5-hydroxytryptophan (5-HTP) after inhibition of aromatic L-amino acid decarboxylase with NSD 1015. During asphyxia there was a decrease in tryptophan hydroxylase activity in the whole brain and various regions studied. The levels of tryptophan, 5-HTP and 5-HT all increased after 30 min of recovery from asphyxia. In the whole brain, 5-HTP and 5-HT levels were normal 2 h after anoxia while tryptophan levels normalized more slowly to reach control values after 6 h. In the regional brain study, the 5-HTP levels returned quickly to control levels after asphyxia in the striatum and midbrain but not in the brainstem and hemispheres regions. The whole brain 5-HTP and 5-HT levels did not differ from controls 24 to 48 h after the asphyxia. Although the neonatal nervous system exhibits a great resistance to asphyxia, the metabolism of the neurotransmitter 5-HT is affected already during a short period of asphyxia and subsequent recovery. As 5-HT is ascribed important neurotransmitter functions, this might be relevant to the neurological sequelae of human asphyxia neonatorum.

5-Hydroxytryptophan↗
PubMed1980

Pressure-volume relationship and fluid content in fetal rabbit lung after beta-receptor-stimulating drugs.

A considerable interest has been focused on the effects of various drugs on fetal and neonatal pulmonary maturation and adaptation. In the present study, we have investigated the effects of the selective beta1- and beta2-receptor-stimulating agents prenalterol and terbutalilne on the pressure-volume relationship and fluid content in fetal rabbit lung at 28 days of gestation. Pressure-volume recordings during deflation showed significantly increased lung volumes at equivalent transpulmonary pressures in terbutaline-treated fetuses as compared to controls. No such effect was noted after prenalterol. In the control animals, wet lung weight/body weight ratio decreased to a steady state level 60 min after birth, indicating a rapid dehydration of the lungs. This dehydration was present at delivery after terbutaline and prenalterol treatment. The amount of fluid collected from the airways was also reduced after terbutaline and prenalterol treatment. The present results indicate facilitated neonatal respiratory adaptation after especially terbutaline treatment. Possible mechanisms behind these effects are discussed.

Adrenergic beta-Agonists↗
PubMed1980

The effects of beta-adrenergic receptor blockade on the inhibition of gastric acid secretion, and the release of pancreatic polypeptide by antral distension in healthy subjects.

In a randomized double-blind study of seven healthy subjects an intravenous injection of metoprolol and propranolol did not change the submaximal gastric acid response to pentagastrin. The inhibition of pentagastrin-stimulated acid secretion by balloon distension of the antrum was unchanged by a preceding intravenous injection of metoprolol or propranolol. The plasma level of pancreatic polypeptide in peripheral venous blood showed a significant rise during antral distension. This rise was unaltered by a preceding injection of metoprolol and slightly depressed by propranolol. We conclude that the inhibitory effect of antral distension on gastric acid secretion in healthy subjects is not mediated by beta 1 or beta 2-adrenergic mechanisms. The reflex release of pancreatic polypeptide by antral distension may possibly involve a weak beta 2-adrenergic component.

Adrenergic beta-Antagonists↗
PubMed1980

Prevalence and treatment of hypomagnesemia in the elderly studies in a representative in 70-year-old population and in geriatric patients.

Within in the framework of the longitudinal gerontological and geriatric population study in Göteborg, Sweden, S-Magnesium (S-Mg) was examined in 55 70-year-old males and 55 70-year-old females with a as many probands without diuretic treatment. Probands with diuretic treatment had lower S-Mg than others (p smaller than 0.001). Females had higher S-Mg values than males both in those with (p smaller than 0.05) and without (p smaller than 0.01) diuretic treatment. Sixteen per cent of the males and 7 per cent of the females with diuretics had S-Mg below 0.7 mmol/l compared to none in those without. Out of 161 geriatric inpatients those 50 (17 males and 33 females) with the lowest S-Mg values took part in a double blind comparison between supplementation with a magnesium chloride and a placebo solution during three weeks. The daily dose was 12.5 mmol MgCl2. The tolerance of the solution was tested in 30 young healthy individuals and was found to be good. During treatment with magnesium chloride, S-Mg increased 0.09 plus or minus 0.08 mmol/l (p smaller than 0.001) and during treatment with placebo 0.08 plus or minus 0.09 mmol/l (p smaller than 0.01). The difference between the two groups was not significant. S-potassium, however, increased significantly more in the patients treated with magnesium chloride (p smaller than 0.01). The increase in the treatment group was 0.31 plus or minus 0.32 mmol/l compared to a decrease of 0.02 plus or minus 0.42 mmol/l in the placebo group.

Adult↗
PubMed1980

Plasma levels and pharmacological effects of metoprolol administered as controlled release (Durules) and ordinary tablets in healthy volunteers.

The bioavailability, plasma levels and pharmacological effect of a daily dose of 0.2 g of metoprolol in Durules and in regular 0.1 g tablets have been studied in eight healthy volunteers during steady state conditions. Durules and two 0.1 g metoprolol tablets were given once daily, and one 0.1 g metoprolol tablet was given every 12th hour. The maximum concentration of metoprolol in plasma after Durules was about half of that after two regular tablets. When one metoprolol 0.1 g tablet was administered every 12th hour, an average maximum concentration slightly higher than for the Durules was recorded about one hour after the administration. The minimum concentration of metoprolol during the day was about twice as high after Durules as after the same dose in regular tablets. The dose-corrected area under the plasma concentration vs time curve of Durules was 87 per cent of the b.i.d. regimen of metoprolol in regular tablets and about 75 per cent of two metoprolol 0.1 g tablets once daily. Metoprolol Durules maintained a more even effect on heart rate and systolic blood pressure during exercise during the day than the corresponding daily dose of metoprolol given as two metoprolol 0.1 g tablets once daily or as one metoprolol 0.1 g tablet every 12th hour. After maximum beta-blockade the effect declined by, on average, 0.60 per cent/hour for the Durules and 0.96 per cent for the regular tablet. The exercise heart rate before the morning dose was significantly lower during treatment with Durules and one metoprolol 0.1 g tablet b.i.d. than during the placebo period. The interaction of metoprolol with the effect of adrenaline (0.09 microgram x kg-1 x min-1, infused at 2, 3.5 and 5 hrs after metoprolol administration) on the diastolic blood pressure was more pronounced when two ordinary 0.1 g metoprolol tablets were administered once daily than for the corresponding dose in Durules, this probably reflecting a difference in degree of action of metoprolol on the vascular bed for Durules and regular metoprolol tablets in identical doses.

Administration, Oral↗
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↗