PubMed Health⌕ Search

Biomedical subjects

C Kamei

Publications and source records attributed to C Kamei.

At least 109 records · Page 6Linked to original sources
PubMed1990

Central effect of the potent long-acting H1-antihistamine levocabastine.

The effects of levocabastine (R 50 547; CAS 79516-68-0) on the central nervous system were studied in comparison with those of diphenhydramine, ketotifen and azelastine. At high doses, levocabastine caused a decrease in locomotor activity, prolongation of thiopental-induced sleep, depression of acetic acid-induced writhing in mice and inhibition of active avoidance response in rats, but these adverse effects were much less potent than those seen in diphenhydramine, ketotifen and azelastine. Oxotremorine-induced tremor and salivation in mice were delayed after extremely high dosage of levocabastine; however, these were much less effective than those seen after diphenhydramine and ketotifen. Levocabastine did not affect the tonic extensor seizure induced by maximal electroshock in mice which is different from that of diphenhydramine. In EEG analysis, levocabastine at a dose of 20 mg/kg caused no significant changes in the EEG recorded from the frontal cortex, occipital cortex, hippocampus and amygdala in rats with chronic electrodes.

Acetates↗
PubMed1990

Histamine lipolysis II: effects of histamine and related compounds on membrane potentials of rat adipocytes.

The effects of histamine (Hi) and related compounds on rat mesenterial adipocytes were investigated using electrophysiological techniques. Hi caused a concentration-related depolarization and significant effect was observed at concentrations higher than 5 x 10(-6) M. Effective membrane resistance was also decreased by Hi. The H1-agonists 2-methylHi and 2-thiazolylethylamine caused no depolarization even at a concentration of 5 x 10(-4) M, but the H2-agonists, 4-methylHi and impromidine decreased resting membrane potentials. While 4-methylHi was less potent than Hi, impromidine was more potent. The H1-antagonists diphenhydramine and pyrilamine did not affect Hi-induced depolarization. However, H2-antagonists like cimetidine and ranitidine caused a significant inhibition even at a concentration of 10(-6) M. As in the case of isoproterenol, the decrease in resting membrane potentials induced by Hi was significantly potentiated by theophylline. Dibutyryl cyclic AMP treatment and intracellular application of cyclic AMP also caused a marked depolarization.

Adipose Tissue↗
PubMed1988

The effects of H1- and H2-receptor blocking agents on postsynaptic potentials recorded from the bull-frog sympathetic ganglion.

The effects of H1-blockers (pyrilamine, diphenhydramine and promethazine) and H2-blockers (cimetidine, ranitidine) on the postsynaptic potentials of the bull-frog sympathetic ganglion were studied by means of the sucrose gap method. All the H1-blockers tested, at concentrations of 10(-6)-10(-4) M, depressed the amplitudes of both action and slow postsynaptic potentials in positive and negative directions in a concentration-dependent manner; these drugs had more potent inhibitory effects on postsynaptic potentials. In the case of H2-blockers, action and postsynaptic potentials were slightly depressed as perfusion continued at 10(-4) M. From the present experiments, it was concluded that H1-blockers directly inhibit postsynaptic potentials of the sympathetic ganglions, and that this inhibition may be responsible for various autonomic disturbances attributed to H1-blockers.

Action Potentials↗
PubMed1987

The effects of cephem antibiotics and related compounds on the aldehyde dehydrogenase in rat liver mitochondria.

The effects of cephem antibiotics and their related compounds on aldehyde dehydrogenase obtained from rat liver mitochondria were studied. A pH of 8.8 and reaction temperature 24 degrees were the conditions for measurement of enzyme activity. The apparent Michaelis constant Km values for NAD, acetaldehyde and propionaldehyde were 3.8 X 10(-5) M, 4.0 X 10(-5) M and 2.5 X 10(-5) M, respectively. Cefamandole, cefoperazone and cefmetazole, having a 1-methyl-5-thiotetrazol group at position 3 of the cephem ring, caused a relatively potent inhibition of aldehyde dehydrogenase. Cefmetazole and cefoperazone also showed a significant inhibition on highly purified yeast aldehyde dehydrogenase; the extent of inhibition on yeast enzyme was almost the same as that on rat mitochondrial aldehyde dehydrogenase. The decrease in enzyme activity effected by 1-methyl-1H-tetrazol-5-thiol (MTT) was greater than those of 1H-tetrazol (TZ), 1H-tetrazol-5-thiol and 1-(2-dimethylaminoethyl)-1H-tetrazol-5-thiol, but was, of course, less than that of disulfiram. Cefamandole, cefmetazole and MTT showed competitive inhibition with NAD, while TZ was uncompetitive inhibitor with respect to both NAD and acetaldehyde. Enzyme inhibition caused by disulfiram, cefmetazole and MTT increased time-dependently and the addition of 2-mercaptoethanol into the medium effectively and completely restored enzyme inhibition. These results suggest that thiol group at position 5 of 1H-tetrazol ring is responsible for the type of inhibition with NAD, and methyl group at position 1 of 1H-tetrazol ring is important to exhibit a potent inhibition on aldehyde dehydrogenase.

Aldehyde Dehydrogenase↗
PubMed1987

Immunological studies on delayed hypersensitivity to phenytoin--I. A new method for preparing phenytoin antiserum.

The present study was initiated to produce an antiserum to phenytoin with high specificity and sensitivity which would be suitable not only for determination of blood phenytoin concentration but also for induction of a hypersensitivity reaction to phenytoin in experimental animals. p-Aminophenytoin was synthesized and identified by means of IR, 1H-NMR and mass spectroscopy. BSA-phenytoin conjugate was prepared by using p-aminophenytoin, BSA and, as a coupling reagent, glutaraldehyde. Satisfactory response to immunization was achieved at a 9.8:1 molar ratio of p-aminophenytoin to BSA. The antiserum obtained from rabbits immunized with BSA-phenytoin conjugate exhibited practically no cross-reactivity with either phenytoin metabolites or other anti-epileptic drugs, indicating that this antiserum provides sufficiently high specificity. In our experiments, the lower limit for detecting phenytoin was 2 ng using RIA, whereas 200 ng was the minimum amount detectable by HPLC. Thus, by a difference of two orders of magnitude, the present RIA method shows a much higher sensitivity than that of HPLC, though we found a good correlation of simultaneous determinations of serum phenytoin between the two methods. Reproducibility of phenytoin determination in plasma was confirmed by calculating the coefficient of variance. The values were less than 10%.

Animals↗
PubMed1987

Immunological studies on delayed hypersensitivity to phenytoin--II. The delayed skin reaction induced by BSA-phenytoin conjugate.

Remarkable swelling of the foot pad was induced in guinea pigs sensitized with BSA-phenytoin by challenging with BSA-phenytoin or EA-phenytoin. Forty-eight hours after local injection of a mixture of exudate cells obtained from the abdominal cavity of sensitized guinea pigs. and BSA (EA)-phenytoin, both erythema and induration developed at the injection sites in normal guinea pigs. At the sites exhibiting these skin reactions, an exudation of mononuclear leukocytes was noted. In addition, macrophages obtained from the abdominal cavity of phenytoin-sensitized animals showed a low migration index in the presence of phenytoin. When phenytoin was administered to rats (p.o.), large amounts of the compound were detected in the gingiva and there was a good correlation between the tissue and serum phenytoin concentrations. These findings indicate that the etiology of gingival hyperplasia produced by chronic administration of phenytoin may be related in some way to a delayed-type hypersensitivity induced by the drug.

Animals↗
PubMed1987

Effects of antihistamines on the spinal reflex in rats.

The effect of antihistamines on the spinal reflex in rats was studied. When H1-blocking agents such as pyrilamine, promethazine and diphenhydramine were given intravenously, both monosynaptic reflex (MSR) and polysynaptic reflex potentials (PSR) were inhibited in a dose-dependent fashion without affecting the dorsal root reflex and dorsal root-dorsal root potential. The extent of suppression of the MSR and PSR measured in spinal rats was smaller than that of intact rats. When H1-blocking agents (0.25-5.0 nmol) were applied by intraspinal microinjection close to the motoneuron, the MSR and PSR were depressed dose-dependently. Simultaneous application of carbachol partially blocked the inhibitory effects of H1-blocking agents induced by intraspinal microinjection. Also, the motoneuron discharges evoked by microinjection of glutamic acid or acetylcholine were depressed by simultaneous administration of any of H1-blocking agents tested. However, H2-blocking agents, such as cimetidine and ranitidine, given either intravenously or intraspinally had a scarcely measurable effect on the spinal reflex. The depression of H1-blocking agents on the spinal reflex is due to a direct inhibition of the motoneuron on the one hand. On the other hand, there is also an involvement of higher centers in the central nervous system increasing potential depression.

Animals↗
PubMed1987

Antihypertensive effects of nisoldipine and reference drugs in certain types of hypertensive rats.

The hypotensive effects of nisoldipine (Bay K 5552), compared with those of nifedipine, nicardipine and hydralazine, in normotensive rats (NR), spontaneously hypertensive rats (SHR), DOCA-NaCl hypertensive rats (DNR) and renal hypertensive rats (RHR), were studied. The changes in plasma renin activity (PRA) after treatment with nisoldipine and these reference drugs were also studied. The results of this study revealed that: 1. Nisoldipine caused more potent antihypertensive effects in SHR, DNR and RHR than in NR. 2. The antihypertensive effects of nisoldipine in SHR were almost equipotent to those of nifedipine, nicardipine and hydralazine. However, in NR, DNR and RHR, the effects of nisoldipine were weaker than those of the reference drugs. 3. The positive chronotropic effects of nisoldipine were less remarkable than those elicited by nifedipine, nicardipine and hydralazine in all types of hypertensive rats, except SHR. 4. As did nifedipine and nicardipine, nisoldipine caused an increase of the plasma renin activity in NR and SHR, though its potency was weaker than those of nifedipine and nicardipine.

Animals↗
PubMed1986

Effects of various cephem antibiotics on ethanol metabolism and their structure-activity relations.

The effects of various cephem antibiotics and related compounds on ethanol metabolism were studied in association with their chemical structures. In rats, cefoperazone, cefbuperazone, cefamandole, latamoxef, cefmetazole, cefotetan, cefmenoxime and cefminox which have the [(1-methyl-1H-tetrazol-5-yl) thio] methyl group at position 3 of the cephem ring caused a significant increase in the blood acetaldehyde concentration. In the last three compounds, disulfiram-like activity was less potent than that evaluated in the preceding compounds. Cefazolin and ceftezole having a 1H-tetrazol group at position 7 also showed a disulfiram-like activity. A single administration of 1H-tetrazol also increased the blood acetaldehyde concentration. Both blood ethanol and acetaldehyde values were increased significantly on administration of these drugs. In beagle dogs, cefoperazone induced a less remarkable but much more sustained increase in the blood acetaldehyde. These results indicate that the 1H-tetrazol group, as well as the [(1-methyl-1H-tetrazol-5-yl) thio] methyl group, is responsible for inducing a disulfiram-like action and that there is a difference in the potency of the disulfiram-like activity among the drugs having a [(1-methyl-1H-tetrazol-5-yl)thio] methyl group at position 3 of the cephem ring in relation to those in which the side chain is substituted at position 7.

Acetaldehyde↗
PubMed1986

Influence of histamine and related compounds on the hypnotic effect of thiopental in mice.

Intraventricular injection of histamine (Hi) significantly prolonged thiopental sleeping time at doses of 0.5 microgram or larger. Both 1-methylHi and imidazole-4-acetic acid, however, did not affect thiopental narcosis. Pretreatment with alpha-fluoromethylhistidine diminished the effect of Hi, while histidine, metoprine and quinacrine prolonged thiopental narcosis. Injection with 2-methylHi did not affect thiopental sleeping time, while as in the case of Hi, 4-methylHi augmented the thiopental effect. In addition, H2-receptor blocking agents such as cimetidine, ranitidine and famotidine clearly antagonized Hi-induced prolongation of thiopental narcosis, while pyrilamine and chlorpheniramine had no effect. These results indicate that Hi-induced prolongation of thiopental narcosis appears to be exerted via H2-receptors and is, in some way, related to the Hi content in the brain.

Animals↗
PubMed1986

Comparative study of various H1-blockers on neuropharmacological and behavioral effects including 1-(2-ethoxyethyl)-2-(4-methyl-1-homopiperazinyl)benzimidazole difumarate (KB-2413), a new antiallergic agent.

In a conditioned avoidance response tested in rats, all of the H1-blockers employed caused a dose-related inhibition at doses 5-20 mg/kg (i.v.) except for ketotifen that elicited significant suppression even at a dose of 1 mg/kg. No inhibition was seen after administration of 1-(2-ethoxyethyl)-2-(4-methyl-1-homopiperazinyl)benzimidazole difumarate (KB-2413). ED50s were ranged from 4.1 to 7.4 mg/kg in diphenhydramine, pyrilamine and promethazine. In laminectomized rats, diphenhydramine, pyrilamine, promethazine and ketotifen suppressed the amplitudes of monosynaptic reflex potentials at doses higher than 2 mg/kg (i.v.). In the case of chlorpheniramine, significant inhibition was observed at a dose of 20 mg/kg. In a polysynaptic reflex, similar but less prominent inhibitions were affected by those drugs. However, KB-2413 did not influence spinal reflexes even at a dose of 20 mg/kg. In the rat phrenic nerve-diaphragm preparation, perfusion of H1-blockers at a concentration of 10(-5) M decreased the amplitudes of end-plate potentials except for chlorpheniramine and KB-2413. At 10(-4) M, all the test drugs caused significant inhibition. When the action potential of superior cervical ganglion was measured by the sucrose gap method, promethazine inhibited the action potential significantly at 10(-6) M, but the rest of the test drugs depressed the potentials at 10(-5) M. In spontaneous EEG, all H1-blockers caused a marked drowsy pattern at lower doses (2-5 mg/kg) except for chlorpheniramine, while in higher doses (10-20 mg/kg) epileptic signs in EEG with or without convulsive behavior were noticed. However, after KB-2413 (5-20 mg/kg) neither drowsy nor seizure pattern was observed, in EEG or behavior.

Action Potentials↗
PubMed1986

Pharmacological profiles of 2-carboxyphenyl-1-(4-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetate and 2-[(2-carboxyphenoxy)-carbonyl]phenyl-1-(4-chlorobenzoyl)-5-meth oxy-2- methylindole-3-acetate, new antiinflammatory agents.

When the effects of new antiinflammatory drugs, 2-carboxyphenyl-1-(4-chlorobenzoyl)-5-methoxy-2-methyl-indole-3-acetate (TB 219) and 2-[(2-carboxyphenoxy)carbonyl]phenyl-1-(4-chlorobenzoyl)-5- methoxy-2-methylindole-3-acetate (TB 220), were investigated in various experiments, the following results were obtained: 1. TB 219 and TB 220 showed remarkable inhibitory effects on carrageenin edema, ultraviolet erythema and adjuvant arthritis. Although TB 219 displayed almost equipotent or slightly more potent effect than those of indometacin and acemetacin, TB 220 was slightly less effective than these two reference drugs except for the therapeutic effect on adjuvant arthritis. 2. TB 219 and TB 220 inhibited the writhing syndrome induced by acetic acid and inflammatory hyperesthesia, and they provided a significant antipyretic activity. 3. Both drugs elicited almost negligible side effects in the gastrointestinal tract even after the repeated administrations. Especially, ulcerogenic activity of TB 220 was extremely weak. LD50's of both drugs are higher than that of indometacin in rats. 4. Both drugs elicited no appreciable changes in general behavior in mice and rats after oral administration. After intraperitoneal or intravenous injection of these two drugs, no marked changes in spontaneous EEG pattern and the spinal reflex were observed.

Animals↗
PubMed1985

The effects of histamine and some related compounds on conditioned avoidance response in rats.

When histamine (Hi) and other agonists were applied intraventricularly, Hi caused a dose-dependent inhibition of the avoidance response in rats; its ED50 was 3.60 micrograms. 1-methylHi, 1-methylimidazole acetic acid and imidazole acetic acid which are major metabolites of Hi produced no inhibitory effect even at 50 micrograms. H1-agonists (2-methylHi and 2-thiazolylethylamine) also depressed the avoidance response; their dose-response lines run parallel to that of Hi. The depressant effects of H2-agonists (4-methylHi and dimaprit) were relatively weak; their dose-response lines were not parallel to that of Hi. When antagonists were pretreated intravenously, Hi action was clearly antagonized by diphehydramine and pyrilamine, but not by cimetidine or ranitidine. Intraventricular injection of Hi mixed with cimetidine or ranitidine did not change the effect induced by Hi alone. The avoidance response was not affected by noradrenaline, dopamine or 5-hydroxytryptamine. Although acetylcholine (ACh) suppressed the avoidance response dose-dependently, its effect was much weaker than that of Hi. Pretreatment with cholinergic blocking drugs (atropine and scopolamine) antagonized ACh action but not Hi action. From these results, it is assumed that the inhibitory effect of Hi on the avoidance response is preferentially linked to the H1-receptor. After intraventricular application of 3H-Hi, the highest radioactivity was determined in the hypothalamus.

Acetylcholine↗
PubMed1985

Hypotensive effects of dihydropyridine derivatives.

Effects of six dihydropyridine derivatives (nifedipine, nisoldipine, nitrendipine, nicardipine, nimodipine and niludipine) and hydralazine on blood pressure and heart rate in spontaneously hypertensive rats (SHR) were studied in comparison with those in normotensive rats (NR). Nisoldipine, nitrendipine and nicardipine showed stronger hypotensive effect in SHR than in NR. All the dihydropyridine derivatives--especially nifedipine, nitrendipine and niludipine--lowered blood pressure of SHR at doses smaller than those producing positive chronotropic effect. Hydralazine caused hypotensive effect in the same extent both in SHR and in NR and, moreover, it brought about tachycardia at doses smaller than those lowering blood pressure.

Animals↗
PubMed1984

Analgesic effect of histamine induced by intracerebral injection into mice.

Three methods were used to study the analgesic effect of intracerebral injection of histamine (Hi) on mice: the writhing test (acetic acid and phenylquinone), the electrical stimulation of the tail and the hot plate test. At doses higher than 2 micrograms, Hi inhibited the writhing syndrome significantly, and at doses of 10 micrograms or higher, Hi displayed a marked analgesic effect during both the electrical stimulation and hot plate methods. The saline injection produced only a negligible effect. Simultaneous application of Hi and 10 micrograms of diphenhydramine, pyrilamine or promethazine, apparently causing no analgesic effect from a single administration, caused a parallel shift of the dose-response curve of Hi to the right. ED50 of Hi was increased approximately 2, 2.8 and 3.8 times, respectively. However, cimetidine did not reveal any antagonistic effect on Hi-induced analgesia. Subcutaneously administered, 3 mg/kg of morphine augmented the analgesic effect of Hi. In accordance with this, pretreatment of naloxone (0.005 mg/kg) antagonized the analgesic action of Hi almost completely. When 5 mg/kg of leucine-enkephalin, less than the minimum effective dose, was given prior to Hi injection, the analgesic effect of Hi was enhanced. In addition, 10 and 20 micrograms of Hi increased the morphine analgesia markedly and parallel shifted the dose-response curve of morphine to the left.

Analgesics↗
PubMed1984

Epileptogenic activity induced by intravenous injection of certain cephalosporins in rats.

Epileptogenic activity induced by intravenous injection of certain cephalosporin derivatives was studied. Ceftezole provided the most potent epileptogenic activity among the drugs tested. Changes in seizure patterns on electroencephalogram (EEG) tracings and behavioral signs after administration of cefotiam and cefazolin were similar to those seen after ceftezole, though the intensity and duration were less than those of ceftezole. Cephacetrile and cephaloridine elicited the spiking activity in the frontal cortex and the other regions without apparent behavioral changes. Latamoxef and cefmenoxime displayed a weak epileptogenic activity at a dose of 1000 mg/kg. On the other hand, cephapirin, cefmetazole and cefoxitin did not evoke any changes in EEG nor in behavior. Penicillin G at a dose of 200 mg/kg affected spike or spike-and-wave complex in a few cases, but at a dose of 500 mg/kg the animals died of dyspnea almost immediately after injection without showing apparent epileptogenic signs. These results suggest that some of cephalosporins such as ceftezole, cefotiam, cephacetrile and cefazolin provide epileptogenic activity at higher doses.

Animals↗
PubMed1984

Excitatory and inhibitory effects of H1-blockers on isolated bullfrog spinal cords.

Effects of pyrilamine and diphenhydramine on isolated spinal cords of bullfrogs were studied in order to clarify the mechanisms of depressant and stimulant actions of H1-blockers on the central nervous system. Pyrilamine and diphenhydramine depressed both the DR-VRP and DR-DRP. Pyrilamine and diphenhydramine also suppressed L-glutamate-induced depolarization of the motoneurones, but they did not depress GABA depolarization at the dorsal root terminals. By switching the perfusate to drug-free Ringer solution, depressed amplitudes of DR-VRP were suddenly increased over the control level (rebound phenomenon). The rebound increase of DR-VRP was inhibited by either tetrodotoxin or D-600. These results suggest that the rebound phenomenon may be due to the effect of H1-blockers 1) inhibiting transmitter release participating in presynaptic inhibition and 2) inducing a rapid recovery from the depressed influx of Na+ and Ca2+ into motoneurones.

Animals↗