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Biomedical subjects

H H Frey

Publications and source records attributed to H H Frey.

At least 91 records · Page 5Linked to original sources
PubMed1978

Pharmacokinetics of ethosuximide in the dog.

The pharmacokinetics of ethosuximide were studied in dogs and compared with the data known for man. After intravenous injection of 40 mg/kg to 9 dogs, the concentration-time curve in serum could be described by the open one-compartment model. Serum half-lives were between 11 and 25 hr, the volume of distribution correspond to between 44 and 66% of body weight. After oral administration of the same dose, maximal serum concentrations were reached within 1-4 hr and the absorption amounted to 88-95%. By treatment with three daily doses, a plateau in serum concentrations could be reached and maintained. At serum concentrations above 100 microliter/ml, half-lives seemed prolonged when compared to the values determined previously with a dose of 40 mg/kg. Ethosuximide rapidly enters the cerebrospinal fluid, equilibrium was established after 20-30 min. Plasma protein binding of the drug was negligible. Comparison of the pharmacokinetic data for dog and man reveals, in spite of the somewhat shorter half-life in the dog, a rather good agreement. In female rats, ethosuximide had an average half-life of 10 hr, in mice of hardly 1 hr. Concentrations in serum and brain of mice equilibrated within 10 min.

Administration, Oral↗
PubMed1977

Effect of convulsant and anticonvulsant agents on level and metabolism of gamma-aminobutyric acid in mouse brain.

1. The effect of the convulsant agents pentetrazole, picrotoxin, bicuculline, strychnine and isoniazid on the central level of gamma-aminobutyric acid (GABA) and the activity of the enzymes glutamate decarboxylase (GAD) and GABA-alpha-oxoglutarate aminotransferase (GABA-T) from mice brain was studied in vivo and vitro. In vivo, convulsant doses of picrotoxin and isoniazid lowered the level of GABA and the activity of GAD, whereas strychnine and bicuculline had no such effect. Pentetrazole inhibited GAD, but did not alter the GABA content. In vitro, all convulsants, except bicuculline, inhibited the activity of GAD; however, the concentrations of strychnine were far beyond the range that is reached in vivo by convulsant doses. Only isoniazid inhibited the activity of GABA-T in vivo as well as in vitro. 2. Phenobarbital, ethosuximide and trimethadione were about equally active in preventing convulsions induced by strychnine and picrotoxin, whereas diazepam was 9 times, and sodium valproate 3.5 times more active against convulsions elicited by picrotoxin. Phenytoin up to 100 mg/kg was ineffective against all chemoconvulsants. 3. Diazepam, sodium valproate, ethosuximide and trimethadione antagonized the inhibition of GAD and the decrease in GABA concentrations caused by isoniazid. Phenobarbital and phenytoin prevented the decrease of GABA but did not reverse the inhibition of GAD. 4. The results suggest a role played by the transmitter pool of GABA in the convulsant action of chemoconvulsants and in the anticonvulsant effect of antiepileptics clinically used in petit mal epilepsy.

4-Aminobutyrate Transaminase↗
PubMed1977

Study into the mechanism of acetylsalicylic acid-induced bronchoconstriction.

In order to elucidate the mechanism of the acetylsalicylic acid-induced bronchoconstrictor responses which have been observed in asthmatic patients, experiments were done in cats, anesthetized by chloralose, vagotomized, and completely relaxed by infusion of suxamethonium. In about half of the experiments, the sensitivity of the bronchi to 5-hydroxytryptamine (5-HT) was considerably enhanced after the administration of 5--6 mg/kg acetylsalicylic acid, a dose which had previously been shown to suppress prostaglandin (PG) biosynthesis in the bronchi of the cat completely. No further increase in sensitivity to 5-HT occurred when higher doses of the drug were given. Immediate bronchoconstrictor reactions to the injection of acetylsalicylic acid were rare, in most instances the rise in sensitivity developed slowly during a period of about 30 min. The results are consistent with the assumption that PGE2 displays an antagonistic effect to the mediators of asthmatic bronchoconstriction or to their liberation and that inhibition of PG synthesis by acetylsalicylic acid or related drugs eliminate this function and may thus give rise to bronchospasm.

Animals↗
PubMed1977

[On the mechanism of action of valproid acid].

In mice, the influence of valproic acid (di-n-propylacetate, DPA) on central level of gamma-aminobutyric acid (GABA) as well as the activity of the enzymes regulating GABA metabolism, glutamate decarboxylase (GAD) and GABA-alpha-oxoglutarate aminotransferase (GABA-T) were studied. It was shown that the elevation of GABA by DPA was accompanied by an activation of GAD. GABA-T was inhibited only by toxic doses or high concentrations of DPA in vivo and in vitro, and so was GAD. DPA proved able to antagonize the biochemical alterations induced by convulsant doses of isoniazid, i.e., decreases in the level of GABA and the activity of GAD. These results point to a role of the transmitter pool of GABA regulated by GAD in the anticonvulsant effect of DPA.

4-Aminobutyrate Transaminase↗
PubMed1977

Concentrations of acidic antiinflammatory drugs in gastric mucosa.

In rats, the concentrations of the acidic antiinflammatory drugs salicylic acid, acetylsalicylic acid, phenylbutazone, flufenamic acid and indomethacin in the glandular portion of the gastric mucosa were determined 30 and 60 min after oral or subcutaneous administration. In another series of experiments, solutions of the drugs were introduced into the ligated stomach and the concentrations in the mucosa and in the contents of the stomach were determined after 60 min. The ratio between the concentrations in the musoca and those in serum or gastric contents were much lower than expected according to the distribution by passive non-ionic diffusion. This apparent discrepancy may be explained as a result of a drug-induced damage to the mucosal cell allowing free diffusion of ionized drug across the cell membrane.

Animals↗
PubMed1976

Antagonism of arachidonic acid-induced bronchoconstriction in cats by aspirin-like analgesics.

In cats, anesthetized with chloralose, vagotomized and relaxed by infusion of sexamethonium, bronchoconstrictor reactions were induced by the i.v. injection of arachidonic acid (50 to 200 mug/kg). These reactions could be completely suppressed by the following drugs: indomethacin (ED50 0.16 mg/kg), flufenamic acid (1.8 mg/kg), acetylsalicylic acid (2.4 mg/kg) and phenylbutazone (4.7 mg/kg), but paracetamol was only partly effective even in doses up to 50 mg/kg. The results show that rather small doses of most weak analgesics can effectively inhibit prostaglandin biosynthesis in the bronchi and make it likely that this inhibition is involved in the drug-induced bronchoconstrictor reactions, which have been observed clinically.

Acetaminophen↗
PubMed1976

Di-n-propylacetic acid--profile of anticonvulsant activity in mice.

The anticonvulsant effect of di-n-propylacetic acid (n-DPA) was studied in mice and compared to those of phenobarbital, trimethadione and ethosuximide. n-DPA was only weakly active in the maximal electroshock test, but had an ED50 of 420 mg/kg orally in the pentetrazole seizure threshold test, which corresponds rather well to the activity of trimethadione and ethosuximide. The duration of action was only short, and the first signs of neurotoxicity--inability to perform in the chimney test--appeared well below the anticonvulsant ED50 against pentetrazole. n-DPA proved to be most active against convulsions induced by picrotoxin (ED50 200 mg/kg orally), which might indicate a role of the elevation of the central levels of gamma-aminobutyric acid in the anticonvulsant effect of the drug.

Animals↗
PubMed1976

Use of bumetanide, a potent diuretic, to obtain urinary samples for dope testing in horses.

Use of the potent, high-ceiling diuretic bumetanide made it possible to obtain urinary samples for dope testing of trotters within the 1st hour after the race. The drug was injected intravenously at a dose level of 10 mug/kg during the cold season of the year, but on warm days, a dose of 20 mug/kg was more reliable. These doses did not produce any side-effects and did not interfere with the detection of doping drugs, since bumetanide is not metabolized to a detectable degree and the unchanged drug appears only in extracts from acidic urine. By enhancing the clearance of drugs used for doping, bumetanide even provides favorable conditions for detection of such drugs.

Amphetamines↗