Search PubMed⌕ Search

Biomedical subjects

H Jacobi

Publications and source records attributed to H Jacobi.

At least 37 records · Page 2Linked to original sources
PubMed1983

Increase in cerebrospinal fluid pressure in dogs due to coronary agents.

Narcotised mongrel dogs were used to examine the effect of coronary drugs on the cerebrospinal fluid pressure (CFP). An increase in CFP, although of varying degree, was observed for all compounds tested. The reason for this effect is suggested to be a direct dilatation of the cerebral blood vessels, leading to an increase in intracranial blood volume. It could be established that the increase in CFP is not due to changes in cardiac or circulation parameters, nor to effects of the volume or osmolarity of the test substance solutions. Thus, the headaches which occur following treatment with dipyridamole or organic nitrates cannot be explained in terms of an increase in CFP.

Animals↗
PubMed1982

[Pharmacokinetics of Morocromen in animals and man (author's transl)].

Investigations in animals (rat, rabbit, dog) and man show, that N-[3-(2-morpholinoethyl)-4-methyl-2-oxo-2H-1-benzopyran-7-yl]-4-morpholinocarboxamide (morocromen) is absorbed fast and is found as unchanged substance in organs (highest concentration in liver and kidneys, low concentration in brain), blood, bile, urine, saliva, sweat and feces. Extent of absorption, metabolisation and half-life are species-dependent. Five metabolites were found in rat, three in dogs and two in traces in man. After oral application unchanged morocromen is excreted renally by rat, dog and man (14, 18 and 54--64%, respectively). Renal elimination is pH-dependent, but not dependent on sex, dosis and urine volume. Oral bioavailability is approx. 60% in dogs, 67--79% in man. Elimination half-life (blood) is approx. 2 h in dogs, 3--4 hr in man. Organ distribution studies in animals and elimination studies in man (1 to 30 applications) give no hint for accumulation or enzyme induction. Morocromen is distinctly different from carbocromen by a longer biological half-life, by distribution and elimination as mostly unchanged drug and by a better bioavailability.

Animals↗
PubMed1981

[Gas-liquid chromatographic determination of etofenamate/ Determination, method and use in biological material (author's transl)].

Etofenamate in biological specimen can be determined by gas-liquid chromatography with etofenamate benzyl ether as internal standard. Determination in urine is done directly after extraction and concentration, whereas plasma and homogenates from organs have to be prepurified by thin-layer chromatography. Unchanged etofenamate is found in small amounts in human urine (0--4, 6--6, 6--8 h p. appl.). Inflamed rat paws after local application contain up to 75 microgram etofenamate/g in comparison to only 2 microgram flufenamic acid/g tissue. Both compounds are also found in non-inflamed paws, contents being only 3--4% as compared to the inflamed tissue. Elimination of etofenamate from the inflamed area occurs with a half-life of approx. 8.5 h. These results from gas-liquid chromatography correspond to results from t.l.c./fluorescence measurements.

Animals↗
PubMed1981

[Studies on metabolism and elimination of etofenamate by dogs (author's transl)].

Renal elimination of etofenamate was studied after oral (200--1200 mg/kg) and intravenous (75 mg/kg) application to dogs. Free flufenamic acid and total fenamates (except phenolic metabolites) were determined. In accordance with other N-arylanthranilic acid derivatives after etofenamate only small amounts are renally eliminated; these results are specific for dog and differ to other animal species. Renally eliminated amounts (up to 8%) are not dependent on dose, the i.v. results also being in the same range. Proportions of free flufenamic acid is small in comparison to total fenamates. Renal elimination occurs preferentially on the first day after application. Biliary elimination of etofenamate and its metabolites was investigated after intravenous as well as intragastric application. Intact etofenamate was found after i.v. and i.g. application, part of it being conjugated. Hydroxyderivatives of Etofenamate (eto) were identified: 5-OH-eto (i.v. and i.g.), 4'-OH-eto (i.v.) and the 5.4'-dihydroxy-eto (i.g.). A further eto-derivative found after i.v. application could not be characterized. Amounts of flufenamic acid (flu) and its hydroxyderivatives (esp. 5-OH-flu) were increased after hydrolytic degradation. These results show that metabolic degradation does not occur primarily be conversion to flufenamic acid; etofenamate itself is degraded by hydroxylation and/or conjugation and subsequent formation of the corresponding flufenamic derivatives.

Animals↗
PubMed1981

[Metabolism of etofenamate / Identification and analytic of metabolites, their pharmacological properties and species dependence of metabolism (author's transl)].

After oral application of etofenamate to animals (rat, rabbit, dog, monkey) unchanged etofenamate and numerous metabolites are found in urine. Analytical properties (thin-layer chromatographic behavior, UV- and fluorescence data) of etofenamate, 5-hydroxy-, 4'-hydroxy, 5,4'-dihydroxy-etofenamate, flufenamic acid, 5-hydroxy-, 4'-hydroxy-, 5,4'-dihydroxy-flufenamic acid are described. Derivatives of etofenamate and flufenamic acid are excreted by rabbit, dog, monkey and man, whereas flufenamic acid derivatives are excreted preferentially by rats; profound degradation takes place in dogs. Metabolism in man is more similar to monkey than to dog and rodents. Metabolic pattern after oral and cutaneous application is quite similar. The six hydroxy derivatives have no pharmacological activity--they do not contribute to the pharmacological action of the substance.

Animals↗
PubMed1981

[Interaction of coronary-active compounds and anti-inflammatory drugs on the coronary vascular system (author's transl)].

The effect of acemetacin (Rantudil) and indomethacin, respectively, on coronary flow and O2-pressure in coronary sinus blood before and after i.v. injections of coronary active compounds was permanently registered in anesthetised closed-chest dogs. It was found that i.v. infections of 2 mg acemetacin/kg extended effects of i.v. injected morocromen. After administration of morocromen (4.0 mg/kg), carbocromen (2.0 mg/kg), or dipyridamole (0.4 mg/kg) the application of acemetacin or indomethacin, respectively, produced a markedly increased effect on the coronary blood vessels. Comparative studies of indole-derivatives, the Ca-antagonizing compounds prenylamine, verapamil, nifedipine, and the phosphodiesterase inhibitor papaverine showed no similar effects.

Animals↗
PubMed1980

[Analytical methods and in vitro studies with acemetacin].

1. Analytical methods (isolation, TLC, UV-spectroscopic and preferably fluorimetric determination) of [1-(p-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetoxy] acetic acid (acemetacin, TV 1322, Rantudil), its analogues, hydrolysis-products and metabolites from biological material are described. 2. Stability is also dealt with. Hydrolysis of the p-chlorobenzoyl group results in strongly fluorescing compounds and can be used in determination of acemetacin, indometacin and derivatives 3. Proof is given that in in vitro studies, such as e.g. Mizushima's protein turbidity test or the test for inhibition of prostaglandin-synthetase, only intact acemetacin (and none of its potential break-down products) is present and is active. 4. In in vitro studies, such as the inhibition of total complement and of the increase in activity of serum sulfhydryl groups, acemetacin and a series of its salts proved to be at least as effective as indometacin. 5. In comparing protein binding, acemetacin, like indometacin, is found to bind strongly to albumin. The portion of free, non-protein bound acemetacin, which thus remains available for the pharmacological action, is found to be approx. 60% higher than the corresponding portion of free indometacin.

Animals↗
PubMed1980

[On the pharmacodynamics of acemetacin (author's transl)].

Pharmacodynamic studies were carried out on (1-(p-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetoxy]acetic acid (acemetacin, TV 1322, Rantudil), a new strongly acting non-steroidal anti-inflammatory agent for elucidation of its mechanism of action. Despite its strong anti-inflammatory activity, acemetacin is only a weak inhibitor of prostaglandin release. Release of histamine from mast cells induced by N-methylhomoanisylamine-formaldehyde condensate (compound 48/80) was strongly inhibited by acemetacin in a dose dependent manner. It was also highly effective in in vitro tests, for example, in the protein turbidity test of Mizushima. In accordance to the weak inhibition of prostaglandin release very little damage was done to the mucous membrane of the gastrointestinal tract by this anti-inflammatory agent. From these data and from the strong anti-inflammatory activity a broad therapeutic margin can be derived. Analgetic properties were shown in the benzoquinone test after oral and in the Randall-Selitto test after i.m. application. Hyperthermia caused by Pyrifer and by yeast is inhibited by acemetacin in a dose dependent manner. Corresponding to the weak influence on prostaglandin release the reduction of diuresis by acemetacin was only small. No tocolytic effect could be detected on the gravid uterus in vitro. Function of the heart (isolated heart of guinea-pig) was unaffected, but we registered an increase in sytolic and diastolic blood pressures in the anesthetized dog. Correspondingly, left ventricular pressure also increased, these changes were accompanied by bradycardia. Coronary flow, peripheral flow and dp/dt did not change, only the pressure in the right atrium rose slightly. In cats, acemetacin caused a short-lasting decrease in the arterial blood pressure. Effects on CNS were not found. Smooth muscles (bronchial/intestinal) were not influenced by acemetacin. Like many non-steroidal anti-inflammatory compounds acemetacin inhibits also platelet aggregation. Motility of animals was lowered. In a granuloma pouch test a strong anti-inflammatory action was shown in vivo even without metabolic degradation of acemetacin. For the explanation of the anti-inflammatory action several mechanisms have to be taken into account.

Animals↗
PubMed1980

[Chemical structure and anti-inflammatory activity in the group of substituted indole-3-acetic acids (author's transl)].

The chemical structure of the indometacin molecule was systematically modified with the aim of producing a substance with increased anti-inflammatory activity and improved tolerance. In addition to the variations of the methylene group of the indole-3-acetic acid and substituents on the indole nucleus of indometacin, particular attention was paid to the modification of the carboxyl group of the acetic acid side chain. Among the indometacin esters, one derivative, the [1-(4-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetoxy] acetic acid (54), showed an activity approximately twice that of indometacin in the kaolin edema test in the rat paw. Chemical modification of the new compound 54 did not further improve the activity. These studies suggest that specific substitutions on the indole nucleus, in combination with the acetic acid side chain as in 1, and especially the acetoxy acetic acid side chain in 54 are responsible for the high anti-inflammatory activity of this class of substances. Several methods for the synthesis of acemetacin are described.

Animals↗
PubMed1980

[Anti-inflammatory action of acemetacin (author's transl)].

The anti-inflammatory efficacy of [1-(p-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetoxy]acetic acid (acemetacin, TV 1322, Rantudil) a new non-steroidal anti-inflammatory agent, is described. The stronger inhibition of inflammation in kaolin-induced edema of the rat paw could experimentally be proved with the new compound in comparison with a series of marketed anti-inflammatory agents. Acemetacin is highly effective following both oral and parenteral administration. Following provocation of inflammation in the rat paw by a series of other different agents acemetacin was more strongly effective than indometacin following oral administration. Clear advantage of acemetacin as against indometacin were shown after influencing Freund's adjuvant induced arthritis. In local inflammation too, for example in the wool pellet test, the development of granulation tissue and exudate was inhibited to the same extent as following application of corticosteroid. Both skin erythema and dye-stuff spreading by inhibition of hyaluronidase were antagonised. From the results obtained with acemetacin in numerous inflammatory models conclusion can be drawn as to the multiple sites of action in the reaction chain of inflammation.

Animals↗