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Biomedical subjects

R Kretzschmar

Publications and source records attributed to R Kretzschmar.

At least 37 records · Page 2Linked to original sources
PubMed1984

Pharmacological studies on propafenone and its main metabolite 5-hydroxypropafenone.

The new antiarrhythmic drug propafenone and its main human metabolite 5-hydroxypropafenone were investigated for antiarrhythmic, local anaesthetic, Ca++-antagonistic and beta-adrenoceptor blocking effects as well as for their activity on the central nervous system. In isolated organs (guinea-pig atria, rat aortic strips) 5-hydroxypropafenone had a smaller effect on the maximum following frequency, a greater negative inotropic effect, a greater Ca++-antagonistic effect and a very distinctly weaker beta-adrenoceptor blocking effect than propafenone. Consistent with its antiarrhythmic potency in vitro, intra-cutaneous 5-hydroxypropafenone had a smaller local anaesthetic effect in the guinea pig wheal. In contrast to these findings 5-hydroxypropafenone showed a stronger antiarrhythmic potency in vivo (rat and dog), as demonstrated on the aconitine- and infarction arrhythmias. In addition, in His bundle studies 5-hydroxypropafenone caused a more marked prolongation of the conduction time in atria, AV-node and His-Purkinje system. In vivo the beta-adrenoceptor blocking effect of 5-hydroxypropafenone (isoprenaline tachycardia, rat) was smaller than that of propafenone. The difference between the in vitro and in vivo potency of 5-hydroxypropafenone may be explained by differences in pharmacokinetics, e.g. by a smaller distribution volume compared to propafenone. CNS effects were investigated due to local anaesthetic properties of the substances tested. As indicator of CNS activity anticonvulsant effects, detectably beneath convulsion-inducing doses, were determined in rats (max. electroshock seizures). The results show low CNS activity of propafenone which is even lower for the metabolite but which is distinctly higher for lidocaine and - related to the antiarrhythmic potency - for flecainide, too.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthetics, Local↗
PubMed1983

6-Aryl-4,5-dihydro-3(2H)-pyridazinones. A new class of compounds with platelet aggregation inhibiting and hypotensive activities.

This paper reports on the synthesis and pharmacological activity of 6-aryl-4,5-dihydro-3(2H)-pyridazinone derivatives. The compounds exhibit an aggregation inhibiting action on human platelets in vitro and on rat platelets under ex vivo conditions, as well as a hypotensive action on rats. The strongest pharmacological effects were found with dihydropyridazinones, which have a 6-[p-[(chloroalkanoyl)amino]phenyl] substituent, together with a methyl group in the 5-position. The antiaggregation activity of compounds of this type is in vitro up to 16000 times and ex vivo up to 370 times greater than that of acetylsalicylic acid; the hypotensive action is up to 40 times as great as that of the comparative substance dihydralazine.

Animals↗
PubMed1983

[Round atelectasis].

a) For several reasons Sinner's paper calls for critical remarks: His term "Pleuroma" for a neither pleural nor tumorous but intrapulmonary and atelectatic mass lesion lacks any anatomical and histological basis and is misleading at that because it pretends a tumor of the pleura; his statement in the summary that atelectatic pseudotumors of the lung show a tumorcell-like cytoarchitecture is surprising without being further discussed by the author; he encourages risky invasive diagnostical procedures even in cases where the radiological diagnosis of round atelectasis is unmistakable; already known radiologic features of round atelectases are presented by him as hitherto undescribed; his conceptions of the formal development of round atelectases and of their most characteristic features can not be agreed with. b) The different forms of round atelectases and their residuals are presented with tomograms and with diagrams of their formal development from our point of view.

Bronchiectasis↗
PubMed1981

Pharmacology of amezinium, a novel antihypotensive drug. III. Studies on the mechanism of action.

Pharmacological studies on the mechanism of action of 4-amino-6-methoxy-1-phenyl-pyridazinim methyl sulfate (ameziniummetilsulfate, LU 1631, Regulton), in the following briefly called amezinium, are presented. 1. Amezinium increases the arterial blood pressure and heart rate of anaesthetized animals and of pithed rats by stimulating vascular alpha- and cardiac beta 1-adrenoceptors. The action was not modified by ganglionic blockade with hexamethonium. The alpha-adrenergic blocking drug phentolamine antagonized the blood pressure increasing effect and the beta-adrenergic blocking drug propranolol antagonized the heart rate increasing effect. 2. Noradrenaline depletion by pretreatment with reserpine reduced the pressor effect of amezinium to approximately the same extent as it reduced the effect of tyramine. It completely abolished the heart rate increasing effect. Under these conditions, high doses of amezinium reduced the heart rate. 3. Amezinium is taken up by adrenergic neurones. Inhibition of uptake 1 with desipramine reduced the pressor effect of amezinium and of tyramine. 4. Being a substrate of uptake 1, amezinium also inhibited noradrenaline and tyramine uptake. Consequently, it enhanced the pressor effect of exogenous noradrenaline and increased the contractions of the nictitating membrane following preganglionic stimsipramine reduced the pressor effect of amezinium and of tyramine. 4. Being a substrate of uptake 1, amezinium also inhibited noradrenaline and tyramine uptake. Consequently, it enhanced the pressor effect of exogenous noradrenaline and increased the contractions of the nictitating membrane following preganglionic stimsipramine reduced the pressor effect of amezinium and of tyramine. 4. Being a substrate of uptake 1, amezinium also inhibited noradrenaline and tyramine uptake. Consequently, it enhanced the pressor effect of exogenous noradrenaline and increased the contractions of the nictitating membrane following preganglionic stimulation (endogenous noradrenaline). It diminished the effect of indirectly acting sympathomimetic drugs (tyramine). It did not modify the action of the sympathomimetic drugs methoxamine and isoprenaline, which are not subject to uptake 1. 5. Amezinium inhibits monoamine oxidase (MAO). As a result of being concentrated in sympathetic neurones via uptake 1 amezinium causes specific inhibition of intraneuronal MAO; this was demontrated by enhanced restoration of the effects of tyramine and amezinium by noradrenaline infusion in reserpinized animals. The effective doses of amezinium here were lower than the doses necessary to inhibit tyramine and to exert a pressor effect. This is in accordance with the blood pressure increasing effect of amezinium itself by amezinium pretreatment and noradrenaline-infusion. 6. Pretreatment with a MAO inhibitor (nialamide) enhanced the pressor effect of amezinium, probably by also inhibiting extraneuronal MAO...

Animals↗
PubMed1981

Pharmacology of amezinium, a novel antihypotensive drug. VI. Effect on central nervous functions.

4-Amino-6-methoxy-1-phenyl-pyridazinium methyl sulfate (ameziniummetilsulfate, LU 1631, Regulton), in this study briefly called amezinium, was tested for possible central effects taking particular account of the mechanisms of action found for this substance in other studies. 1. The most conspicuous action of amezinium was in modifying reserpine-induced ptosis and reserpine-induced hypothermia. When amezinium is given before reserpine, the ED50 values are 0.15 and 3.9 mg/kg p.o. for both mouse and rat. These effects can be explained by a peripheral site of action since peripheral sympathomimetic effects can also be demonstrated in this dose range. Higher doses (10 mg/kg and upwards p.o.) were required to abolish reserpine-induced hypothermia 17 h after reserpine administration, an effect which probably requires a central site of action. But for imipramine, desipramine and pargyline the effective doses are the same in both experimental models (administration before and after reserpine, respectively). 2. Amezinium potentiated the effect of a threshold dose of L-dopa. Based on the central symptoms, higher doses (10 mg/kg p.o.) were also required for this effect. 3. With blood pressure increasing doses, the sleeping-waking pattern was modified in that duration and number of REM-episodes were reduced; in cats there was no parallel increase of wakefulness whilst in rats there was a slight relative increase of wakefulness. 4. Amezinium, particularly at high doses (46.4 mg/kg and upwards), exhibited a central depressant effect on the spontaneous behaviour of mice and rats and on orientational hyperactivity of mice. Based on the modification of aggregation toxicity, the effect of methamphetamine was reduced. In no dose range was there any evidence of methamphetamine-like effects (increase of motor activity, inhibition of food intake and increase of aggregation toxicity). 5. Amezinium did not affect the duration of hexobarbital anaesthesia or the coordination of mice on a rotating rod. 6. The acute toxicity of amezinium in mice and rats was low. The oral LD50 for mice was 1630 mg/kg and for rats 1410 mg/kg.

Animals↗
PubMed1980

[Pharmacology of N-(2-imidazolin-2-yl)-N-(4-indanyl)amino (indanazoline), a new vasoconstrictive imidazoline compound].

In animal experiments the new imidazoline derivative N-(2-imidazolin-2-yl)-N-(4-indanyl)amine (indanazoline, E-VA-16, as monohydrochloride active substance of Farial) is characterized by a pronounced vasoconstrictive action after local or intravenous application. This is due to a direct action of the compound on alpha-adrenergic receptors. When applied systemically E-VA-16 being a peripherally acting alpha-sympathomimetic induces a rise in blood pressure and a reduction of heart rate and exerts antiphlogistic, spasmolytic, hyperglycemic and diuretic actions. When given by the intranasal route the substance influences blood pressure and heart rate only at concentrations considerably higher than those intended for use in therapy. After enteral administration the effective doses also markedly exceed the single therapeutic doses. There was no evidence of side-effects restricting the use of the drug as compared to other imidazoline derivatives. Studies on the isolated perfused rabbit ear, however, indicated a broader therapeutic range in local application.

Anesthetics, Local↗
PubMed1980

[Chemistry and biological properties of substituted 3-amino-1H-isoindoles (author's transl)].

Several 1-, 3-, and 6-substituted 3-amino-1H-isoindoles have been synthesized and screened for biological properties. In pharmacological testing significant and long-lasting local-anesthetic activity was found even in low concentrations. Subsequently, investigations for antiarrhythmic properties were carried out. The same or even higher activity compared to quinidine sulfate was found on isolated guinea pig atria (refractory period prolongation), anaesthetized rats (aconitine induced arrhythmias), guinea pigs (electrically induced cardiac fibrillation) and in conscious dogs with arrhythmias due to coronary artery occlusion. Unfortunately, antiarrhythmic doses caused toxic symptoms in dogs.

Anesthetics, Local↗
PubMed1977

[The radiology of the dorso-basal part of the chest (author's transl)].

The radiology of the dorso-basal part of the chest includes a number of unmistakable lesions with characteristic appearances. These are demonstrated by a series of appropriate cases (diaphragmatic processes, pulmonary sequestrations, pleural disease and the late effects of a pneumothorax). Their differential diagnosis is discussed.

Adult↗
PubMed1976

[Pharmacological investigations of 4'-fluoro-4-(4-methyl-peperidono)-butyrophenone with respect to its sedative and sleep-inducing properties (author's transl)].

The butyrophenone melperone (Eunerpan) in mice and rats caused a prominetn inhibition of spontaneous activity, whereas cataleptogenic and apomorphine-antagonistic properties were less pronounced. In rats the sleep-cycle was altered: decrease of wakefulness, increase of slow-wave sleep and a moderate reduction of rapid eye movement-(REM) sleep. In contrast to thioridazine and chlorpromazine the effect lasted only for 4 h, followed by a slight REM rebound. In rabbits melperone caused a decrease of muscle tone and with somewhat higher doses an inhibition of the arousal-reaction. As seen by the computerized spontaneous cortical EEG, dosages below 1 mg/kg caused a shift of the dominant frequency from theta- to delta-rhythm and an increase of power. Therefore the neuropharmacological pattern of the butyrophenone melperone is closely related to those of thioridazine or chlorpromazine, without, however, having their long action.

Animals↗
PubMed1976

[Pharmacological investigations with the combination sulfamoxole/trimethoprim, a new broadspectrum chemotherapeutic agent (author's transl)].

Investigations were conducted with the combination of N1-(4,5-dimethyl-2-oxazolyl)-sulfanilamide (sulfamoxole) and 2,4-diamino-5-(3,4,5-trimethoxy-benzyl)-pyrimidine (trimethoprim) (CN 3123, Nevin, Supristol) in a dose ratio of 5:1, with respect to pharmacological activity and possible side effects. The effects obtained with the combination CN 3123 were compared with those of the single substances. In a dose range comparable to that as used in clinical treatment, there were no effects on cardiovascular or respiratory functions, on functions of autonomic and central nervous system, on contractility of smooth muscles and on data of clinical chemistry such as urine and electrolyte excretion, blood sugar, blood coagulation and liver function tests. Doses which are 5 to 10 times higher than the initial dose or 10 to 20 times higher than the maintenance dose used in man caused an increase of urine and sodium excretion without influencing potassium and chloride output. There were no signs of sedation as alteration of motility or EEG patterns, but in mice and rats there was an increase in both duration and depth of anaesthesia caused by barbiturates or ether. Only in a dose range 30 to 40 times higher than the initial dose for man there were some slight alterations with respect to cardiovascular system and liver function tests. In vitro, with high concentrations of CN 3123 there was a weak, unspecific spasmolytic effect on the isolated ureter and an increase in the refractory period of the guinea pig atrium. There were no hints that the side effects seen with separate administration of high or very high doses of sulfamoxole or trimethoprim were increased or poteniated by their simultaneous administration. Slight side effects in animals were only observed with doses exceeding the tenfold of the doses for therapeutic use in men. Therefore, the therapeutic range of CN 3123 seems to be more than adequate.

Animals↗