Biomedical subjects

S Kawano

Publications and source records attributed to S Kawano.

At least 361 records · Page 20Linked to original sources

PubMed1990

[The effect of aldioxa on the formation of gastritis induced with sodium hydroxide].

The effects of aldioxa and cetraxate hydrochloride on the formative process of gastritis induced with intragastric application of 2% sodium hydroxide were studied. Rats were given food including either aldioxa or cetraxate hydrochloride for 6 weeks after the sodium hydroxide application. After sacrifice, the stomachs were removed, and the gastric mucosa were observed macroscopically and histologically. Gastric mucosal injury was widely induced with sodium hydroxide, being histologically characterized by mucosal hypertrophy, cell infiltration and intestinal metaplasia. These lesions seem to be the early stage of chronic gastritis. The aldioxa group showed a decrease of mucosal hypertrophy and cell infiltration as compared with the control group. In the cetraxate hydrochloride group, the mucosal surface of white gray color and the mucosal bosselation were observed macroscopically. Histologically, these were found to be cell infiltration and cyst formation. Moreover, intestinal metaplasia occurred at high incidence in this group. These findings in the cetraxate hydrochloride group are recognized to be an aggravation of chronic gastritis. From the above results, it is suggested that aldioxa promotes good regeneration of mucosa and should be useful for the clinical therapy of chronic gastritis.

Allantoin↗

PubMed1990

[A study on the survival rates for patients and suspected patients with Itai-itai disease].

A follow-up study was carried out from January 1967 to December 1986 on 148 patients with Itai-itai disease, 130 suspected patients (persons requiring observation), and 212 controls who were living in the same community as patients with Itai-itai disease. The relative survival rates for the three groups were calculated from a life expectancy table. Except for 1973 data, comparison of the annual data from 1968 to 1986 showed that the relative survival rates in the patient group were significantly lower than those in the control group. The relative survival rates in the suspected patient group were significantly lower than those in the control group between 1981 and 1986. Recently the differences of the relative survival rates between the patient group and the suspected patient group have become smaller and are not significant. These results show the long-lasting influence of Itai-itai disease on the prognoses of patients and suspected patients.

Adult↗

PubMed1990

[Acute toxicity study of buspirone hydrochloride in mice, rats and dogs].

Buspirone hydrochloride (abbr. to BH), an anxiolytic drug, was examined for its intravenous, subcutaneous or oral acute toxicity using Crj: CD-1 (ICR) mice, Crj: CD (Sprague-Dawley) rats and beagle dogs of both sexes. The results obtained were summarized as follows: 1. Drug-related toxic signs included decreased activity and convulsions accompanied with salivation and opisthotonus in mice and rats treated with BH regardless of administration routes, and tremors and clonic convulsions accompanied with salivation in dogs treated with BH orally. 2. Pathological examinations revealed distention of the stomach in dead rats treated with BH orally, and hypersecretion of gastric juice and alterations (viz. edema, necrosis and petechia) on the superficial mucous membrane in the gastropyloric region in dead dogs treated with BH orally. 3. The cause of death was considered to be due to respiratory insufficiency in every species of animals examined. 4. LD50 values (mg/kg) were as follows: [table: see text] 5. No sex differences were observed in every species of animals regardless of administration routes on the basis of toxicological parameters examined.

Administration, Oral↗

PubMed1990

[Antigenicity study of buspirone hydrochloride in guinea pigs and mice].

Buspirone hydrochloride(buspirone) and buspirone-ovalbumin mixture were examined for their antigenicity in guinea pigs and mice in comparison with ovalbumin (OVA) and 2, 4-dinitrochlorobenzene (DNCB)-OVA conjugate. The results obtained were as follows: 1. When guinea pigs were sensitized with buspirone or buspirone-OVA emulsified with Freund's complete adjuvant (FCA), these animals showed negative reactions in active systemic anaphylaxis (ASA), active cutaneous anaphylaxis (ACA), passive cutaneous anaphylaxis (PCA), passive hemagglutination (PHA) and Schultz-Dale test. 2. When mice were sensitized with buspirone or buspirone-OVA adsorbed to alum, these animals revealed a negative reaction in PCA using rats. 3. As positive controls, guinea pigs were sensitized with OVA or DNCB-OVA emulsified with FCA, and mice with OVA or DNCB-OVA adsorbed to alum. As a result, these animals disclosed positive reactions in ASA, ACA, PCA, PHA and Schultz-Dale test. As shown above, buspirone was considered to possess neither antigenic nor haptenic properties.

Anaphylaxis↗

PubMed1990

[Reproductive and developmental toxicity studies of buspirone hydrochloride (I)--Oral administration to rats during the period of fetal organogenesis].

Buspirone hydrochloride (buspirone), an anxiolytic drug, was administered orally to pregnant Crj: CD (Sprague-Dawley) rats from day 7 through 17 of gestation at dose levels of 2, 12 and 75 mg/kg/day. The summarized results obtained are as follows: 1. Decreased activity was observed for F0 dams at buspirone 75 mg/kg. Further, the suppression of maternal body weight gains accompanied by the reduction of food consumption was shown during the administration period at the same dose level. 2. Liver weights were increased in F0 dams at term at buspirone 12 mg/kg and higher. Besides, brain, pituitary, adrenal and ovarian weights were increased in F0 dams at term at buspirone 75 mg/kg. 3. Buspirone 75 mg/kg brought the inhibition of fetal growth followed by the lowered values in fetal weights, crown-rump distances and tail lengths. Furthermore, the elevated incidence of skeletal abnormalities such as nodular and wavy ribs and unossified 5th and 6th sternum , as well as retarded ossification of cervical vertebrae, forelimbs and hindlimbs were also noted in this dose level. Also, the retarded ossification was observed at 12 mg/kg. 4. Buspirone failed to affect the parturition of F0 dams. 5. Buspirone did not function the viability of newborns (F1), and postnatal differentiations, learning ability, motility, motor activity or emotional development in F1 animals. 6. Body weight gains were depressed in female F1 rats from 4 to 9 weeks of age and food consumption was decreased in male F1 rats from 6 to 8 weeks of age at buspirone 75 mg/kg. 7. Buspirone 75 mg/kg produced suppressions of brain weights at 10 weeks of age in male and female F1 rats and lung weights at weaning in male F1 rats. Spleen weights were increased in female F1 rats at 10 weeks of age at the same dose level. However, buspirone failed to affect their reproductive ability. 8. F2 neonates derived from F1 rats whose dams had ever received buspirone during the period of fetal organogenesis showed no changes in observation items at birth. Based on these results, the no-effect dose level of oral buspirone under the present experimental condition was estimated to be 2 mg/kg/day against dams and their offspring.

Abnormalities, Drug-Induced↗

PubMed1990

[Reproductive and developmental toxicity studies of buspirone hydrochloride (II)--Oral administration to rats during perinatal and lactation periods].

Buspirone hydrochloride (buspirone), an anxiolytic drug, was administered orally to pregnant Crj: CD (Sprague-Dawley) rats from day 17 of gestation through day 20 of postpartum at dose levels of 2, 12 and 75 mg/kg/day. The summarized results obtained are as follows: 1. Decreased activity was observed for F0 dams at buspirone 75 mg/kg. Further, the suppression of maternal body weight gains accompanied by the reduction of food consumption was shown during the administration period at buspirone 12 mg/kg and higher. 2. Brain and adrenal weights were increased in F0 dams at buspirone 12 mg/kg and higher. Besides, lung and pituitary weights were augmented in F0 dams at buspirone 75 mg/kg. 3. Buspirone 75 mg/kg brought the increased number of stillbirths in F1 neonates. 4. Buspirone 75 mg/kg lowered the viability of newborns (F1) on postnatal day 3 and prolonged the days required for pinnae detachment, presence of abdominal hair and eye opening in offspring (F1), but failed to function their learning ability, motility, motor activity or emotional development. 5. Body weight gains were depressed in both male and female F1 rats at buspirone 12 mg/kg and higher. Food consumption was also decreased in both sexes at the same dose levels. 6. Heart weights were decreased in female F1 rats after mating at buspirone 12 mg/kg and higher. Further, buspirone 75 mg/kg brought a suppression of brain weights at 10 weeks of age in male and female F1 rats, but failed to affect their reproductive ability. 7. F2 neonates derived from F1 rats whose dams had ever received buspirone during the perinatal and lactation periods showed no changes in observation items at birth. Based on these results, the no-effect dose level of oral buspirone under the present experimental condition was estimated to be 2 mg/kg/day against dams and their offspring.

Abnormalities, Drug-Induced↗

PubMed1990

Different effect of Helicobacter pylori on the human gastric antral and body mucosal intracellular mucin.

To elucidate the role of Helicobacter pylori infection in the pathogenesis of gastric ulcer, we investigated the intracellular mucin content by measuring the periodic acid-Schiff-Alcian blue (PAS-AB)-stained substances, by means of computer, in the biopsy sample of gastric mucosa from patients with and without H. pylori infection. In the antral mucosa the intracellular PAS-AB-stained mucin content was significantly smaller in patients with infection than in patients without infection, whereas in the oxyntic gland mucosa the intracellular mucin content showed no significant change between patients with and without infection. In an animal study we investigated the effect of ammonia, which might be produced by H. pylori in the presence of urea. The ammonia, administered orally, caused a greater decrease of intracellular PAS-AB-stained mucin content in the gastric antral mucosa than in the body mucosa, in a dose-dependent manner. The results suggested that H. pylori infection had a different effect on the gastric mucosal intracellular PAS-AB-stained mucin and lowered specifically the antral intracellular PAS-AB-stained mucin content, possibly due to generation of ammonia by H. pylori.

Alcian Blue↗

PubMed1990

[Single dose oral toxicity study of BMY-28100 in juvenile rats and dogs].

In order to investigate the single dose oral toxicity of BMY-28100 in juvenile animals, the drug was administered in single doses to 4-day-old and 14-day-old Crj: CD (SD) rats of both sexes at a dose of 2,000 mg/kg, and to 4-week-old beagle dogs of both sexes at doses of 500, 1,000 and 2,000 mg/kg by oral route. The results obtained are summarized as follows: 1. In rats, decreases of the body weight gain were observed for male and female rats treated with the drug on postnatal day 4 through 5 days and 3 days after dosing, respectively. There were no apparent drug-related toxic signs. No deaths occurred during the observation period. Enlargement of the cecum was found in a few rats of both sexes administered the drug on postnatal day 4 or 14. 2. In dogs, watery-mucous diarrhea observed at 2 to 3 hours after dosing in all dose groups was not dose-related. This finding lasted in some dogs till 4 days after dosing. An increased incidence of emesis was induced in all males at 2,000 mg/kg and all females of all dose groups except one female at 2,000 mg/kg. Body weights increased normally for all dogs, but one male at 1,000 mg/kg showed a transient decrease in food consumption. No drug-related histopathological changes were found. Based upon these results, BMY-28100 at 2,000 mg/kg induced no apparent toxic changes in the present experimental conditions. Therefore, the single dose oral toxicity of the drug in juvenile animals appeared to be very slight and generally similar to that in adults.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1990

[Four-week repeated dose oral toxicity study of BMY-28100 in juvenile rats].

In order to investigate the repeated dose oral toxicity of BMY-28100 in juvenile rats, the drug was administered orally to 4-day-old Crj: CD(SD) rats of both sexes at daily doses of 250, 750 and 1,500 mg/kg for 4 weeks. The results obtained are summarized as follows: 1. Soiling around the anus apparently correlated to soft stool or diarrhea was observed at 750 and 1,500 mg/kg and the incidence appeared to be dose-related. Three deaths including 1 death due to cannibalization occurred at 750 and 1,500 mg/kg, but they were considered to have been caused by misadministration. 2. Slightly depressed body weight gains were noted in the 750 and 1,500 mg/kg dose groups during early dosing period. 3. Slightly increased averages of food and water consumption observed predominantly in the 1,500 mg/kg dose group at later dosing period and the recovery period were considered as incidental and unrelated to the treatment. 4. Though average values of some blood chemical parameters were slightly suppressed or elevated compared with those of controls at the completion of the dosing and recovery periods, these differences appeared to be generally within normal ranges and to be irrelevant to the drug treatment. No definitive drug-related changes were detected in hematological examinations and urinalyses. 5. The average absolute and/or relative organ weights of the brain, thymus, lungs and liver from male rats in the 1,500 mg/kg dose group were lower than those of the corresponding organs from controls. However, these findings were not considered to be toxicologically significant because no corroborative changes were detected microscopically. 6. Macroscopic and microscopic examinations demonstrated dilatation of the cecum in a dose-related fashion. This phenomenon has been reported with other antibiotics and appears to be drug-related and reversible caused by an alteration of the gut flora. There were no other microscopic changes that were considered to be related to the administration of the drug. 7. Electron microscopic examination revealed no drug-related changes in the liver and kidneys from rats of the 1,500 mg/kg dose group. Based upon these results, the no-effect dose level of BMY-28100 was estimated to be 250 mg/kg/day for both male and female juvenile rats in the 4-week repeated dose oral toxicity study if the finding of cecum dilatation was not considered.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗

PubMed1990

[Immunological properties of BMY-28100 and cefepime].

Immunogenicity, eliciting antigenicity and cross-reactivity of new cephem antibiotics, BMY-28100 and cefepime, were studied by means of passive cutaneous anaphylaxis (PCA), passive hemagglutination (PHA) and active systemic anaphylaxis in guinea pigs, and of PCA in mice and the results were compared with those obtained with reference antibiotics. In addition, the direct Coombs' reaction of the human blood was examined in vitro for the test antibiotics as compared with reference antibiotics. The results obtained are summarized as follows: 1. Immunogenicity Immunogenicity of unconjugated antibiotics was examined using the corresponding conjugates with bovine gamma-globulin (BGG) as eliciting antigen. When used as emulsions with Freund's complete adjuvant, cephalothin (CET) and benzylpenicillin (PCG) produced IgG1 and IgM antibodies in guinea pigs. However, cefepime as well as cephalexin (CEX) did not produce these antibodies, and BMY-28100 showed slightly active sensitization only for anaphylactic shock. In BALB/c and C3H/He mice, BMY-28100 and cefepime failed to produce antibodies under the experimental condition while IgE antibody formation to CET was observed. 2. Eliciting antigenicity Unconjugated CET and PCG provoked anaphylactic signs in guinea pigs sensitized with their conjugates with rabbit serum albumin (RSA). Cefepime, however, provoked no anaphylactic shock and BMY-28100 as well as CEX showed slight signs. In the other systems examined, no reactions were observed when elicited with BMY-28100, cefepime or the reference antibiotics. 3. Immunological cross-reactivity BMY-28100 did not cross-react with the reference antibiotics. While the antiserum to the RSA conjugate of CET provoked weak cross-reaction on PHA with the BGG conjugate of cefepime, the antiserum to the RSA conjugate of cefepime failed to react with the BGG conjugate of CET. Other cross-reactivities of cefepime were not observed against the reference antibiotics. 4. In vitro direct Coombs' reaction BMY-28100 did not induce the Coombs' reaction of the human blood in vitro at the testable concentration of 10 mg/ml. Cefepime or cefazolin (CEZ) caused no reaction even at a high concentration of 80 mg/ml, while CET and PCG caused a positive reaction at 10-40 mg/ml and 60 mg/ml, respectively. As shown above, immunogenicity and eliciting antigenicity of BMY-28100 and cefepime were somewhat weaker than CET and PCG but similar to CEX, and cross-reactivities of the test antibiotics with these reference antibiotics were not observed in general. The ability of BMY-28100 to give a positive reaction in the Coombs' test was weaker than that of CET, and that of cefepime was weaker than CET and PCG and equivalent to CEZ.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1990

Measurement of retinal adhesive force in the in vivo rabbit eye.

A new method to evaluate the retinal adhesive force, which was defined as the force needed to achieve adhesive failure per unit length, in the in vivo rabbit eye was tested. A small dome-shaped retinal detachment (bleb) was made in the posterior pole by injecting balanced salt solution into the subretinal space. A separate measuring micropipette with a tip diameter of 5 microns was inserted into the subretinal space. The subretinal pressure was measured directly with the resistance servonulling method as the solution was injected repeatedly into the subretinal space. According to Laplace's law, the retinal adhesive force per unit length in normal Dutch rabbits was calculated to be (1.8 +/- 0.2) X 10(2) dyn/cm (n = 87). This value was about five times larger than that reported previously with in vitro peeling methods. The new method will resolve several problems encountered in the previous methods and will allow for the measurement of the retinal adhesive force more physiologically and precisely.

Adhesiveness↗

PubMed1990

[The effects of vortex vein ligation and partial scleral resection on the subretinal fluid resorption].

The effects of the choroidal congestion and lamellar scleral resection on the resorption of the subretinal fluid were studied. Small localized retinal detachments were made in pigmented rabbit eyes by injecting balanced salt solution into the subretinal space. In these control eyes, the subretinal fluid was gradually absorbed and the retina was reattached within 160 +/- 21 min. Choroidal congestion was obtained by ligating a couple of vortex veins. To avoid the effects of IOP on the subretinal fluid resorption, IOP was constantly maintained at 20 mmHg by manometry in all experimental eyes. In these eyes, the resorption time was prolonged about 45% compared with the control eyes. After releasing the choroidal congestion by partial thickness scleral resection, the prolonged resorption time was shortened about 19%, but was still 17% longer than that in the non-treated eyes. The present data suggest that the lamellar scleral resection releases the elevated choroidal tissue pressure and is helpful to evacuate the subretinal space.

Absorption↗

PubMed1989

New observations on the mechanisms of antiarrhythmic actions of disopyramide on cardiac membranes.

Electrophysiologic effects of disopyramide on cardiac membranes were studied using the microelectrode technique applied to papillary muscles and the suction pipette whole-cell clamp method applied to isolated ventricular myocytes from guinea-pig hearts. In contrast to previous reports, the development and recovery from the Vmax blocks of action potentials by disopyramide and lidocaine were best expressed by 2 exponential functions, not 1, suggesting that there might be 2 different processes for the sodium current block. A near-therapeutic concentration (11 microM) of disopyramide depressed Vmax at frequencies of 0.1 to 2.0 Hz decreased action potential amplitude and shortened plateau phase in ventricular myocytes. Action potential duration was prolonged by the drug in most of the preparations but shortened in some. Disopyramide prolonged the refractory period and increased threshold current for excitation. The drug was also shown to depress both the calcium current and the delayed outward potassium current. These multiple actions of disopyramide may explain its variety of antiarrhythmic properties.

Action Potentials↗

PubMed1989

Effect of cigarette smoking on the gastric mucosal blood volume index and hemoglobin oxygenation in man.

The acute effect of cigarette smoking on the gastric mucosal blood volume index and the oxygen saturation of hemoglobin (SO2) in the gastric mucosa was investigated in 12 young male volunteers using reflectance spectrophotometry during endoscopy. Six of these volunteers were habitual smokers who had smoked more than 20 cigarettes a day for more than five years. The others were non-habitual smokers who smoked less than 20 cigarettes a year. The indices of mucosal blood volume and the mucosal blood SO2 level were calculated from the spectra obtained at the lesser curvature of the lower corpus of the stomach before and after cigarette smoking. The indices of mucosal blood volume and mucosal blood SO2 decreased significantly after one to three puffs of cigarette smoking in all subjects as compared to the value before smoking, and the degree of decrease in these parameters was significantly greater in the non-habitual smokers than in the habitual smokers. These results suggest that only one to three puffs of cigarette smoking causes a decrease in the mucosal blood volume and the mucosal blood SO2 which might be related to weakening of mucosal defensive factors.

Adult↗

PubMed1989

Body surface maps of ectopic P waves originating in the left atrium in the dog.

Body surface maps of the P wave in dogs stimulated at various sites on the atria were prepared to find diagnostic signs to detect the origin of left atrial rhythm. Body surface electrograms from 87 points on the thorax and 8-12 points on the epicardial surface of both atria were simultaneously recorded. The body surface P maps disclosed characteristic findings according to whether the site of the stimulation was at the lower right atrium (RA) or the upper, middle, or lower left atrium (LA). In the LA rhythm, the maximum of the P maps moves from the left to the right chest during the later phase of atrial excitation, while it goes from the right to the left in the sinus or the RA rhythm. In the P maps of the rhythm originating in the upper LA, the minimum always stays at a position on the chest above the location of the maximum, while the negative potential areas are above the positive ones. The maps of the middle LA rhythm show that the maximum and the minimum are located horizontally to each other on the chest. The positive and negative areas cover both sides of the chest, separated by zero lines running vertically. In the low LA rhythm, the maximum is always located at a position on the chest above the minimum, and the positive areas are above the negative ones. These results indicate that mapping of the body surface P waves is a valuable method for diagnosing left atrial rhythm and for detecting the approximate location of its origin.

Animals↗

PubMed1989

Calcium-sensitive and insensitive transient outward current in rabbit ventricular myocytes.

1. A suction pipette whole-cell voltage-clamp technique was used to record membrane currents and potentials of isolated ventricular myocytes from rabbit hearts. 2. Transient outward current (Ito) was activated by voltage steps positive to -20 mV, increasing in amplitude with further depolarization to reach a maximum around +70 mV. The current attained its peak within 10 ms and then it inactivated for 100-200 ms. 3. A large portion of Ito still remained after the calcium current (ICa) was blocked when depolarizing pulses were applied at a frequency of 0.1 Hz or less. Therefore, this current component is referred to as calcium-insensitive Ito or It. 4. It showed voltage- and time-dependent inactivation similar to that observed in Purkinje fibres and other cardiac preparations. 5. The reversal potential of It depended on external K+ concentration, [K+]o, with a slope of 32 mV per 10-fold change in the presence of a normal [Na+]o (143 mM), while the slope was 48 mV per 10-fold change in low [Na+]o (1.0 mM). 6. It was completely inhibited by 2-4 mM-4-aminopyridine. Ito in the presence of ICa was also partially blocked by 4-aminopyridine and the remainder was abolished by 5 mM-caffeine. 7. The calcium-insensitive and caffeine-sensitive Ito differed in their decay rates as well as in their recovery time courses. The former was predominantly available at a slow pulsing rate, while the latter increased its amplitude with high-frequency depolarization. 8. The caffeine-sensitive Ito was inhibited by a blockade of ICa, by replacing Ca2+ with Sr2+, by external application of ryanodine and by internal application of EGTA. This indicates that the current is calcium-sensitive and is dependent on increased myoplasmic Ca2+ through Ca2+ influx via the sarcolemma and Ca2+ release from the sarcoplasmic reticulum. The current is therefore designated as IK, Ca. 9. The physiological functions of IK, Ca and It are indicated by their contribution to ventricular repolarization at fast and slow heart rates, respectively.

4-Aminopyridine↗

PubMed1989

Low-threshold current is major calcium current in chick ventricle cells.

Single myocytes were dissociated from the apical ventricles of 14-day-old chick embryos and were maintained in culture for 24 h. Isolated rounded cells, 13-18 microns in diameter with input capacitance averaging 5.2 pF, were selected for whole cell patch-clamp analysis of calcium current (ICa). Two current components, T-type (IT) and L-type (IL), were identified by differences in their voltage thresholds and pharmacological sensitivity, IL was activated by depolarizing steps from -40 mV and was selectively blocked by 1 microM D 600 (methoxyverapamil). IT was obtained by subtracting IL from total ICa and was blocked by 120 microM Ni2+. Identified by threshold potential, sensitivity to Ni2+, or resistance to D 600, IT had a greater current density than has been reported in any adult cardiac tissue. It was also larger than IL and was therefore the major contributor to ICa in this preparation.

Animals↗

PubMed1989

Amantadine-induced afterpotentials and automaticity in guinea pig ventricular myocytes.

The ionic mechanisms of amantadine-induced changes in membrane potential and automatic activity in guinea pig ventricular myocytes were studied using the suction-pipette whole-cell clamp method. While 25-100 microM amantadine decreased the action potential amplitude and duration, 200 and 400 microM amantadine lengthened the action potential duration and decreased the maximum diastolic potential with an appearance of diastolic depolarization and automaticity. In the presence of 25-100 microM amantadine, the preparations developed an afterpotential due to incomplete repolarization and a delayed afterdepolarization that eventually brought about triggered automaticity. The former type of afterpotential was abolished by tetrodotoxin (TTX) and the latter by Co2+. Spontaneous activity from the diastolic depolarization was also abolished by Co2+ but not by Cs+. Amantadine suppressed the calcium current to as much as half of the control at the concentrations used (25-200 microM). The drug also produced a depression of the inward rectifier K+ current. The outward current showing time-dependent decay was activated at the plateau voltages by concentrations lower than 100 microM, whereas the delayed outward K+ current was depressed by the drug in a concentration-dependent manner at more positive potentials. Amantadine activated the TTX-sensitive and TTX-insensitive inward currents on repolarization from depolarized states, without producing the transient inward current. These results indicate that the amantadine-induced diastolic depolarization and afterpotentials are caused by changes in multiple ionic currents and that, therefore, the drug can be used as a unique model for the study of arrhythmogenesis.

Amantadine↗