Biomedical subjects
Publications and source records attributed to K Aikawa.
Explore the source record for details and available documents.
KB-509, a new derivative of benzodiazepines, increased locomotor activities of mice in doses of 8-32 mg/kg (p.o.) and a decrease occurred with higher doses. This drug was 3-6 and 1-2 times more potent than diazepam (DZP) and nitrazepam (NZP), respectively, in anticonvulsant (anti-pentylenetetrazol, bemegride, strychnine) activities, antiaggressive activity and potentiation of chlorprothixene-induced hypnosis in mice. On the other hand, KB-509 possessed similar potency to DZP and NZP in muscle relaxant activity in mice and inhibition of flexor in cats, and was markedly weaker than DZP and NZP in causing a loss of righting reflex in mice. In the spontaneous EEG activity, KB-509 induced a drowsy pattern and slightly inhibited arousal response to EEG in rabbits, as did DZP. In particular, KB-509 was more potent than DZP in suppressing the amygdala afterdischarge and had a longer duration of action. KB-509 and DZP slightly depressed body temperature, the cardio-respiratory system and the gastrointestinal tract in high doses. Potentiation of spontaneous motility of the uterus and increase of urine excretion were also observed with high doses. In conclusion, KB-509 is superior to both DZP and NZP in the ratio of anticonvulsant and/or taming activities and muscle relaxant activity, and has a weak central depressant activity.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Studies were conducted to determine the in vivo effect of acetaminophen (AAP) on the lipid peroxidation, drug metabolizing enzyme activity and microsomal electron transfer system of rat and mouse liver. AAP was found to inhibit ethylmorphine N-demethylase activity in the presence of NADPH and this inhibition of the enzyme was due to decrease in cytochrome P-450 content, but not due to change in lipid peroxidation in liver microsomes. Kinetical data showed that AAP administration had no effect on Km values of ethylmorphine N-demethylase, however, a decrease in the Vmax values was seen in rats and mice. There was no significant effect of AAP on both NADPH-cytochrome c reductase and the content of cytochrome b5 3 hours after this administration to rats and mice. On the other hand, AAP induced a significant decrease in NADH-ferricyanide reductase in mice, but not in rats. The greatest decrease in cytochrome P-450 observed among the components of the liver microsomal electron transfer system of rats and mice.
Enzymic depletion of glutathione (GSH) in vitro by aniline analogs was mostly dependent on the cytochrome P-450 level in liver microsomes. In a case of acetaminophen (AAP), active metabolite of AAP formed through liver microsomal drug metabolizing enzymes consumed GSH. The active metabolite formed binds, at least in part, covalently to liver microsomal proteins. In addition, species differences in the extent of GSH depletion by AAP in vitro was related to the amounts of the active metabolite of AAP bound covalently to liver microsomal protein(s) by experiments using 14C-AAP. Similar depletion of GSH was also seen with other aniline analogs such as aniline itself and p-chloroaniline, but not with acetanilide, in four animal species. These in vitro results obtained here strongly support the well-known findings concerning both GSH depletion and covalent binding in vivo of the active metabolite after AAP treatment.
Explore the source record for details and available documents.
Effects of lyophilization and storage of liver 9,000xg supernatant fraction on the activity of drug metabolizing enzymes in some species of animals were studied. Imipramine metabolizing enzyme activity and the content of cytochrome P-450 were stable for, at least, one month without any loss of the activity when lyophilized liver 9,000xg supernatant fraction of some animal species, i.e., rat, mouse, guinea pig, rabbit and dog, was stored under reduced pressure in a deep freezer (-20 degrees C). There were no differences of imipramine metabolism between lyophilized liver 9,000xg supernatant fraction which was kept in a deep freezer for one month and a fresh fraction which was prepared immediately before determinations of the enzyme activity and cytochrome P-450. The data presented here indicated that the lyophilized preparation of the liver 9,000xg supernatant as well as the fresh preparation can be used for the determination of the drug metabolizing enzyme activity.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.