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Biomedical subjects

B Lemmer

Publications and source records attributed to B Lemmer.

At least 145 records · Page 8Linked to original sources
PubMed1982

High-performance liquid chromatographic method for the quantitative analysis of the aryloxypropanolamines propranolol, metoprolol and atenolol in plasma and tissue.

A simple and rapid high-performance liquid chromatographic method is described for the quantitative analysis of three beta-receptor blocking drugs of similar molecular structure (aryloxypropanolamines, AOPAs) but with different polarities. the method consists of extraction, reversed-phase ion-pair chromatography and fluorometric detection, whereby slight modifications in these parameters allow analysis of the different AOPAs in a similar way. The method was used to determine concentrations of propranolol, metoprolol and atenolol in plasma and various organs of the rat. In samples of 1 ml of plasma and 0.5--1.7 g of tissue, drug concentrations of at least 2 ng/ml and 5 ng/g, respectively, can be measured. Extension of the method to other AOPAs is possible.

Animals↗
PubMed1982

[Pharmacological basis for the therapy of cardiovascular disease with beta-adrenoceptor blocking drugs (author's transl)].

The introduction of beta-adrenoceptor blocking drugs initiated a breakthrough in the treatment of various cardiovascular disorders within the last 20 years. The major cardiac indications for beta-blockers are coronary heart disease, hypertension and arrhythmias. No one beta-adrenoceptor blocking drug has been shown to be more efficacious than another, and efficacy can be related to the stereo-selective blockade of adrenergic beta-receptors. The major side effects and the contraindications are mainly due to beta-adrenoceptor blockade in combination with the organ-specific distribution of beta 1- and beta 2-adrenoceptors. In addition to their specific antagonism beta-receptor blocking drugs can differ in beta 1-adrenoceptor selectivity, intrinsic sympathomimetic activity (ISA) as well as in nonspecific effects. However, these ancillary properties do not seem to be of importance for the therapeutic effect of these drugs. A relative beta 1-selectivity is probably able to reduce the incidence of side effects e.g. in asthmatics, in diabetic patients and in patients with peripheral vascular disease, however, beta-adrenoceptor antagonists should be used with caution in these patients, At the present time, there is no convincing evidence that beta-adrenoceptor antagonists with partial agonist activity are superior in patients with congestive heart failure or in asthmatics. Except at high dosages the nonspecific local anaesthetic or cardiodepressant effects of lipophilic beta-adrenoceptor antagonists (propranolol-oxprenolol-group) also do not seem to be of importance in the therapy of cardiovascular diseases. On the other hand, lipophilicity of a lipophilic beta-adrenoceptor antagonists of the propranolol-oxprenolol-group exhibit serum half-lives in the range of two to six hours, whereas half-lives of six to 24 hours are found with the hydrophilic compounds sotalol, practolol, nadolol and atenolol, respectively, while with regard to lipophilicity and serum half-lives timolol, metoprolol, pindolol and acebutolol fall midway between these extremes. It was well established that the duration of action of the beta-adrenoceptor antagonists is about two or three times longer than would be expected from the pharmacokinetic data. This can be explained by the fact that the pharmacodynamic effect obeys zero order kinetics whereas the decline in serum concentration follows first order kinetics. The pharmacokinetic and pharmacodynamic data of the beta-adrenoceptor blocking drugs are of great value in the therapy inasmuch as the dosage interval must be modified accordingly: whereas the lipophilic compounds have to be taken two to four times per day, one dosage per day seems sufficient with the hydrophilic compounds.

Adrenergic beta-Antagonists↗
PubMed1981

Strain-dependency in motor activity and in concentration and turnover of catecholamines in synchronized rats.

Circadian rhythm in motor activity was studied with an Animex motimeter in six strains of rats (ACI, BH, BS, DA, LEW, TNO) synchronized by a 12 hr light: 12 hr dark cycle. ANOVA revealed significant interstrain differences in motor activity as well as in the concentration and turnover of central noradrenaline and dopamine. Strain-dependent differences were also found with regard to tyrosine hydroxylase inhibition on motor activity. However, no significant interstrain correlations were found between endogenous concentration and/or turnover rates of the catecholamines and motor activity in normal and drug-treated rats.

Animals↗
PubMed1980

Antagonism by chlorisondamine and propranolol, but not by atenolol, of the circadian phase-dependent phentolamine-induced changes in the cardiac noradrenaline turnover in the rat.

The effects of phentolamine alone or in combination with propranolol, atenolol and chlorisondamine were studied on the concentration and turnover of noradrenaline in the heart of light-dark (L:D = 12:12 h) synchronized rats. In order to detect possible circadian phase-dependent variations in the drug effects, the same experiments were performed in the light-period and dark-period, respectively. The parameters of the turnover were calculated from the exponential decline of i.v. injected 3H-(-)-noradrenaline. Phentolamine significantly decreased the noradrenaline concentration during L, but not during D. Reduction in 3H-noradrenaline accumulation by phentolamine was 42.3% during L and 22.2% during D. Phentolamine increased the turnover rate of cardiac noradrenaline more than 3-fold in either photoperiod. Chlorisondamine reversed all the effects of phentolamine studied. Propranolol, but not atenolol, antagonized the effects of phentolamine in a dose-dependent and stereospecific way, being more effective when applied during D. Thus, the chronopharmacological studies in unrestrained rats show a circadian phase-dependency of the effects of adrenoceptor blocking drugs. It is concluded that a central site of action is responsible for the antagonism by propranolol of the phentolamine-induced increase in the turnover of the cardiac noradrenaline in vivo.

Animals↗
PubMed1979

Diurnal rhythms in noradrenaline turnover and motility after reserpine and 6-hydroxydopamine.

Experiments were performed in male Wistar rats synchronized by controlled conditions of light (0700--1900 hr) and of darkness (1900--0700 hr). Separately in each photo-period the effects of reserpine or 6-OHDA on the cardiac noradrenaline turnover. Whereas peripheral chemical sympathectomy did not greatly affect the diurnal rhythm in the motor activity were investigated. Initial depletion of the cardiac noradrenaline after acute application of either drug was significantly greater when injected at 2000 hr compared to 0800 hr. In both photo-periods the cardiac turnover of noradrenaline was increased after peripheral chemical sympathectomy with 6-OHDA as well as after amine depletion with reserpine. Inhibition of the protein synthesis had no effect, ganglionic blockade by chlorisondamine on the other hand abolished the rhythm in the motor activity, subacute treatment with reserpine differently affected motor activity in both photo-periods, depending on the time of drug application within 24 hr of a day. The results show that diurnal variations in the levels of neuronal and of motor activity are able to influence drug effects and have thus to be taken into account in animal studies.

Animals↗
PubMed1978

Diurnal variations in the motor activity of the rat: effects of inhibitors of the catecholamine synthesis.

The effects of the inhibitor of the tyrosine-hydroxylase H 44/68 and the inhibitor of the dopamine-beta-hydroxylase FLA 63 on the diurnal variations of the motor activity was studied in male Wistar rats, which were kept under standardized conditions of light and darkness (L:D = 12:12 h). The motor activity was continuously registered in groups of 5 rats using a two-channel Animex motimeter. During light FLA 63 (40 mg/kg, s.c.) greatly increased motor activity on acute application and during darkness the physiological elevation in motor activity was further but slightly increased. H 44/68 (200 mg/kg, i.p.) also increased motor activity during light, but in contrast to FLA 63 greatly reduced motor activity during darkness. The results indicate that though dopamine and noradrenaline are involved in the regulation of behavioural components, one or the other catecholamine may play a predominant role at different times of the day. Thus, it seems worthwhile to study the effects of drugs separately during light and during darkness.

Animals↗
PubMed1978

Diurnal rhythm in the central dopamine turnover in the rat.

Under controlled conditions of environmental light and darkness of 12:12 h the turnover of dopamine and noradrenaline in brain of male Wistar rats was studied at different times of the day. The turnover was calculated from the decline of the amine concentrations either after inhibition of the tyrosine-hydroxylase with H 44/68 (200 mg/kg, i.p.) or after inhibition of the dopamine-beta-hydroxylase with FLA 63 (40 mg/kg s.c.). Whereas the noradrenaline turnover showed only slight but not significant variations within 24 h, the turnover of the central dopamine exhibited significant variations with increased turnover rates in the second half of the light and first half of the dark period. Thus, diurnal variations have to be taken into account when studying the effects of drugs on the turnover of biogenic amines in the central nervous system.

Animals↗