Biomedical subjects

K Iseki

Publications and source records attributed to K Iseki.

At least 127 records · Page 7Linked to original sources

PubMed1994

Effect of first-pass metabolism on enantioselective pharmacokinetics after oral administration of (+)-, (-)- and racemic homochlorcyclizine to rats.

The enantioselective relationship between the pharmacokinetics and hepatic metabolism of homochlorcyclizine hydrochloride (HCZ) was investigated using rats. There were no significant differences in blood concentrations between the three forms after intravenous administration (5 mg/kg) of (+)-, (-)- and racemic HCZ. On the other hand, there were significant differences in the pharmacokinetics between (-)- and (+)-HCZ and between (-)- and racemic HCZ after oral administration (50 mg/kg) of these three forms. The Cmax and AUC0-infinity of (-)-HCZ were lower than those of (+)-isomer and racemate, and its CLo was clearly higher than the others. The (+)-isomer and racemate showed no significant differences in their pharmacokinetic parameters. At a lower dose (10 mg/kg), however, no enantiomeric differences were found in the pharmacokinetic parameters of (+)- and (-)-HCZ. Also examined was the cytochrome p-450-dependent-oxidative metabolism of (+)-, (-)- and racemic HCZ in vitro using rat liver 9000 x g supernatant fraction. The in vitro metabolism of (-)-HCZ was extremely fast, compared with those of the (+)-isomer and the racemate. The Vmax in vitro showed a good correlation with the CLo in vivo after oral administration (50 mg/kg) of all three forms of HCZ. In vitro study of enantiomeric inhibition of the metabolism showed that (+)-HCZ was a competitive inhibitor of (-)-HCZ metabolism, with a Ki of 6.96 microM. (-)-HCZ was also a competitive inhibitor of (+)-HCZ metabolism, with a Ki of 20.4 microM.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1994

[Effect of Enterued administration on the intestinal absorption of orally active cefem antibiotics].

The effect of simultaneous administration of Enterued, an elemental diet, which is composed of oligopeptides (egg white hydrolyzate), on the orally active cefems was investigated. Ceftibuten (CETB) administered together with Enterued to man was excreted slower in the urine. AUC from the plasma concentrations of CETB after the oral administration with Enterued was markedly decreased compared to that without Enterued in rat. In contrast, neither urinary excretion of cephalexin (CEX) in man nor the AUC from the plasma profile of CEX in rat was changed by Enterued. Furthermore, the disappearance, tissue accumulation, net absorption of CETB from the rat jejunal loop were significantly inhibited by Enterued. However, the net absorption of CEX has no alternation in the presence of Enterued, although the apparent disappearance decreased on the basis of the diminishment of tissue accumulation. Additionally, Hepan ED, which is an elementary diet composed of amino acids, and the mineral solution containing neither peptides nor vitamins have also exhibited the decreasing effect on the CETB absorption behaviour. These results suggested that the inhibitory effects of Enterued on the absorption of these antibiotics were not due to the inhibition of peptide-transport systems.

Administration, Oral↗

PubMed1994

[Cyclosporine level in blood as monitored by area-under-the-curve (AUC). III. The influence of absorption phase after orally dosing].

The influence of the absorption phase (the time of maximum blood concentration; Tmax) on the pharmacokinetics of cyclosporine (CYA) in the steady state after oral administration was studied in 26 renal transplant recipients. The patients were divided into three absorption phase groups with the Tmax times as follows, group A (n = 26); OH < or = Tmax < 3 h, group B (n = 6); 3 h < or = Tmax < 6 h and group C (n = 11); 6 h < or = Tmax < or = 12 h. CYA (dose; 1.6-15.0 mg/kg/d) was administered orally to all 26 patients (10-52 years, 33.1-74.2 kg) every 12 h. The blood specimens used in this study were collected just before administration (0 h) in the morning and at intervals of 1, 2, 3, 6, 8 and 12 h after administration. The whole blood CYA levels were measured by high-performance liquid chromatography (HPLC) or by fluorescence polarization immunoassay (FPIA) based on a specific monoclonal antibody. There were no significant differences between the three groups in terms of the dosage (mg/kg/d) and area-under-the-curve (AUC). The trough levels (0, 12 h) correlated well to the AUC only in group A (r = 0.842-0.907, p < 0.001). The morning trough levels (0 h) were significantly higher than the night trough levels (12 h) in groups A and B (p < 0.05-0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1993

The transport mechanisms of organic cations and their zwitterionic derivatives across rat intestinal brush-border membrane. II. Comparison of the membrane potential effect on the uptake by membrane vesicles.

Further investigation of organic cation transport mechanisms were continued using rat intestinal brush-border membranes following our previous report. The net uptake of organic cations was superior to that of their zwitterionic derivatives. This result agreed with the absorption behaviour of these compounds from rat intestinal loop. The uptake of tyramine and 5-benzyloxytryptamine was significantly stimulated by the valinomycin-generated K(+)-diffusion potential (inside-negative). On the other hand, the uptake of zwitterionic derivatives was not affected by the valinomycin-induced K(+)-diffusion potential. The voltage-clamped brush-border membrane vesicles exhibited a complete disappearance of the overshoot-uptake of organic cations. Therefore, this permeation mechanism across the intestinal brush-border membrane seems to be different from the well-known H(+)-antiport system of organic cation found in other organs such as kidney and liver, and depends upon an inside-negative H(+)- or K(+)-diffusion potential.

Animals↗

PubMed1993

The diversity of Na(+)-independent uptake systems for polyamines in rat intestinal brush-border membrane vesicles.

Na(+)-independent uptake rate and binding to the membrane surface of polyamines (spermine, spermidine and putrescine) have been characterized using rat small intestinal brush-border membrane vesicles. The uptake of spermine and spermidine was saturable (Km = 30.4 microM and 148.1 microM, respectively), however, putrescine uptake was not saturable up to 8 mM. In contrast, the values of binding to the membrane surface of all polyamines were not saturable in the present studies. In Dixon plot analysis, spermine competitively inhibited the uptake rate of spermidine with a Ki value of 33.8 microM, while the putrescine inhibitory effect on the spermidine uptake rate was non-competitive (Ki = 3.28 mM). These uptake systems were not affected by the valinomycin-induced K(+)-diffusion potential (inside negative). These results suggested that there were two different Na(+)-independent uptake systems for spermine and spermidine, as well as for putrescine, on this membrane. However, they were not the same as the electric potential-dependent uptake system for monocationic compounds. Furthermore, this uptake system for spermine and spermidine might not be a carrier protein, because the intravesicular spermine exhibited no trans-stimulation effect on the uptake of spermidine.

Animals↗

PubMed1993

Enantioselective pharmacokinetics of homochlorcyclizine. III. Simultaneous determination of (+)- and (-)- homochlorcyclizine in human urine by high-performance liquid chromatography.

A method is described for the simultaneous determination of (+)- and (-)-homochlorcyclizine (HCZ) in human urine by high-performance liquid chromatography on a chiral stationary phase of ovomucoid-bonded silica. The pH of the buffer and organic modifier in the mobile phase markedly affected the chromatographic separation. A mobile phase of methanol-0.02 M acetate buffer (pH 4.7) (25:75,v/v) at a flow-rate of 1.0 ml/min was used for the urine assays. The ultraviolet absorption was monitored at 240 nm, and diphenhydramine was employed as the internal standard for the quantitation. (+)-HCZ, (-)-HCZ and the internal standard were eluted at retention times of 15, 25 and 8 min, respectively. The limit of determination for HCZ enantiomers was ca. 50 ng/ml of urine. One of the metabolites in human urine, which was a quaternary ammonium-linked glucuronide, could also be determined in a manner similar to unchanged HCZ after beta-glucuronidase hydrolysis. A pharmacokinetic study was conducted with three healthy volunteers, who each received a single oral dose of racemic HCZ (20 mg). Distinct differences were found between the two enantiomers, particularly in the metabolic process, that is, the urinary excretion as (-)-HCZ-glucuronide within 48 h was ca. four times higher than that of the (+)-isomer. This method should be very useful for enantioselective pharmacokinetic studies of HCZ.

Adult↗

PubMed1993

The transport mechanisms of organic cations and their zwitterionic derivatives across rat intestinal brush-border membrane. 1. Binding characteristics to the bio- and lipid-membranes.

The uptake mechanisms of organic cations such as tryptamine, tyramine, 5-benzyloxytryptamine (BOTA) and their zwitterionic derivatives (tyrosine, tryptophan, 5-benzyloxytryptophan (BOTP)) by rat intestinal brush-border membrane vesicles and liposome containing phosphatidylserine were studied and compared. As compared to their zwitterionic derivatives, uptake rates by rat intestinal brush-border membrane of these three cations were far superior. The binding of cationic compounds to the brush-border membrane was also higher than those of their zwitterionic derivatives. Furthermore, the binding behaviour of BOTA and tryptamine to phospholipid liposome clearly amplified with increasing amounts of phosphatidylserine. In contrast, the contents of phosphatidylserine, a negatively charged phospholipid, exhibited no effects on the binding of zwitterionic derivatives (tryptophan and BOTP). The double-reciprocal plot of tryptamine binding with BOTA to liposome showed competitive inhibition. These results suggest that the binding of organic cations to the membrane lipid has a relatively high specificity despite the absence of membrane protein such as a transport-carrier in the liposome, and that the binding of cationic compounds play an important role in the uptake to the cell membrane systems.

Animals↗

PubMed1993

Transport characteristics of paraquat across rat intestinal brush-border membrane.

The mechanism of absorption of paraquat, which is a type of quaternary ammonium compound (QAC), was studied using rat intestinal loops and brush-border membrane vesicles. Approximately 47% and 37% of radioactively labeled paraquat injected into jejunal and ileal loops disappeared, respectively, after 60 min. Since only a small amount of radioactivity was detected in the mucosal fraction, most of the paraquat that disappeared from the intestinal lumen was considered to have been carried away by the bloodstream, indicating that paraquat absorption was greater than expected. In spite of its low lipid solubility, the uptake of paraquat by brush-border membrane vesicles reflected smooth penetration into the intravesicular space rather than binding to the membrane. According to the increase in extravesicular paraquat concentration, paraquat uptake in the early stage was saturable. Moreover, early paraquat uptake was significantly inhibited by structurally-related QACs such as tetramethylammonium and choline, but not by an endogenous dicationic amine (putrescine). On the other hand, inside-negative membrane potential had no significant effect on the time course of paraquat uptake. From these results, it is suggested that paraquat is absorbed through a specialized mechanism associated with the carrier-mediated transport system for choline on the brush-border membrane.

Animals↗

PubMed1993

Evidence for increased cancer deaths in chronic dialysis patients.

We analyzed longitudinal data on the cancer mortality rate in chronic dialysis patients and in the general population in Okinawa, Japan. In the general population from 1980 to 1990, the mortality rate has been stable at approximately 1.300 males and 0.897 females per thousand persons year, the male to female ratio being 1.45. In the period from 1971 to 1990, we found 91 (4.6%) patients with cancer in a group of 1,982 (824 females and 1,158 males) chronic dialysis patients; forty-nine of the 91 patient (53.8%) died by April 1, 1991. Using the standard mortality rate in the general population, which was obtained for each sex and age class (0 to 34 years, 35 to 44 years, 45 to 54 years, 55 to 64 years, and > or = 65 years), we calculated the relative risk of death from cancer in dialysis patients. The risk ratio in dialysis patients was significantly increased, being 2.48 (P < 0.05) for males and 3.99 (P < 0.05) for females. The mean (+/- SEM) age at the time of death from cancer in the dialysis group was 60.1 +/- 2.0 years in the males and 60.1 +/- 2.1 years in the females; the males were 6.3 years younger than the general population and the females were 9.3 years younger. The proportion of patients with colon cancer (both sexes) and cancer of the uterus and breast (females) was higher in the dialysis patients than in the general population.

Adolescent↗

PubMed1993

Comparing the cell population on different intraocular lens materials in one eye.

We developed a method to evaluate cell adherence to different intraocular lens (IOL) materials in one eye in which we coated one half of the anterior surface of a poly(methyl methacrylate) (PMMA) IOL with poly(dimethyl siloxane), a silicone material. The lenses were implanted in the anterior chamber of rabbit eyes without lens extraction. Postoperative cellular reaction on the IOL surfaces was studied by specular microscopy. The IOLs were fixed in situ, removed from the eyes, and stained with hematoxylin-eosin so we could evaluate the cell population on the silicone and PMMA surface. Fewer cells were scattered on the silicone surface than on the PMMA surface. This method excludes surgical effects and allows a comparison of various IOL materials in the same eye.

Animals↗

PubMed1993

Serum albumin is a strong predictor of death in chronic dialysis patients.

We examined the predictive value of various clinical variables in assessing survival in chronic hemodialysis patients (N = 1,243, 524 females, 719 males) who were under treatment with hemodialysis as of January 1991 in Okinawa, Japan and who were followed up until April 1992. Basal clinical data such as sex, starting date of dialysis, primary renal disease, blood pressure, blood chemistry values, and dialysis prescription data obtained just prior to dialysis were registered at the start of the study. As of the end of April 1992, 104 had died, 16 were transplant recipients, and five had been transferred. Those who died had significantly lower levels of total protein, serum albumin, total cholesterol, triglyceride, BUN, serum creatinine, body weight, body height, diastolic blood pressure, and duration of hemodialysis than those who survived. Older patients and those with diabetes mellitus had a poorer prognosis. A forward stepwise logistic procedure by SAS was used to determine the predictive value of the above clinical variables. With the addition of laboratory variables, the predictive value of diabetes was lost, as the diabetic patients had low serum levels of albumin and creatinine. The standardized coefficient was -0.380 (P = 0.0001) at age of entry, 0.316 (P = 0.0001) for serum albumin, 0.280 (P = 0.0001) for serum creatinine, 0.138 (P = 0.043) for body mass index (BMI), and -0.139 (P = 0.016) for male sex. The prescribed dialysis dose (M2 hr per week) was significantly correlated with serum creatinine (r = 0.48, P = 0.0001), serum albumin (r = 0.135, P = 0.0001) and BMI (r = 0.275, P = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1993

Evidence for high risk of cerebral hemorrhage in chronic dialysis patients.

One-half of the total deaths in chronic dialysis patients are due to cardiovascular disease; however, the precise incidence and relative risk of those compared to normals are not known. Therefore, we sought to determine the annual incidence of cardiovascular disease and relative risk of those on chronic dialysis to the general population. Both the general population (1.2 million, Census 1990) and chronic dialysis patients (N = 1,609) in Okinawa, Japan were studied prospectively from April, 1988, to March, 1991. Diagnosis of stroke was made by symptoms and brain CT scan, and acute myocardial infarction was done by changes in electrocardiogram and serum enzymes. The relative risk (observed/expected ratio) was calculated by using the standardized morbidity rate obtained in both sexes and age-class every 10 years in the general population. Forty-one stroke (8 cerebral infarction, 31 cerebral hemorrhage, and 2 subarachnoid hemorrhage) and four acute myocardial infarction cases were registered during the study period in chronic dialysis patients. The incidence per 1,000 person-year was 11.5 in stroke, 2.2 in cerebral infarction, 8.7 in cerebral hemorrhage, 0.6 in subarachnoid hemorrhage, and 1.1 in acute myocardial infarction. The relative risk compared to normals was 5.2 in stroke, 2.0 in cerebral infarction, 10.7 in cerebral hemorrhage, 4.0 in subarachnoid hemorrhage, and 2.1 in acute myocardial infarction. Cerebral hemorrhage occurred at 10 years younger than that of the general population (P < 0.001) and was associated with high prevalence of hypertension and low levels of serum albumin and cholesterol. Our results confirm the importance of blood pressure control and nutritional status in chronic dialysis patients.

Adolescent↗

PubMed1993

Survival analysis of dialysis patients in Okinawa, Japan (1971-1990).

We analyzed longitudinal data obtained from the initiation of chronic dialysis in Okinawa, Japan. A total of 1,982 patients (824 females and 1,158 males) were registered in the Okinawa Dialysis Study (OKIDS) up to the end of 1990. The number of patients dying, undergoing renal transplantation, or being transferred was 605 (30.5%), 75 (3.8%), and 23 (1.2%), respectively. The mean acceptance rate per million population increased from 19.7 in 1971 to 1975 to 157.4 in 1986 to 1990. The percentage of diabetic patients and the annual gross mortality rate were, respectively 0% and 0.52 (1971 to 1975), 7.3% and 0.12 (1976 to 1980), 14.4% and 0.06 (1981 to 1985), and 24.6% and 0.07 (1986 to 1990). Cox proportional hazard analysis was used to determine the relative risk (RR) for sex, primary renal disease, age at entry, and the year of starting dialysis. The RR for males was 1.09 (1.00 for females) and the 95% confidence interval (CI) was 0.93 to 1.28. The RR for diabetics was 1.88 (95% CI; 1.55 to 2.28) when that for nondiabetics was set at 1.00. The RR (95% CI) for starting dialysis in 1976 to 1980, 1981 to 1985, and 1986 to 1990 was 0.65 (0.59 to 0.72), 0.43 (0.35 to 0.52), and 0.28 (0.20 to 0.38), respectively, when the RR in 1971 to 1975 was taken as 1.00. During the last two decades, the survival of chronic dialysis patients in Okinawa has continued to improve despite the large increase in acceptance rate, the older age of the new patients, and the increase in diabetic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

The transport mechanism of an organic cation, disopyramide, by brush-border membranes. Comparison between renal cortex and small intestine of the rat.

The characteristics of disopyramide uptake in brush-border membrane vesicles isolated from rat renal cortex and small intestine were investigated. Transport of disopyramide into an osmotically reactive intravesicular space was observed with notable binding to the membrane surface. An outwardly directed H+ gradient stimulated disopyramide uptake, resulting in a transient uphill transport in both brush-border membranes. As for the renal brush-border membrane, the H+ gradient itself appeared to be the driving force for this stimulation of uptake. These findings suggest that disopyramide-H+ antiport is the mechanism of disopyramide action in renal cell membrane. The initial uptake was saturable (Km and Vmax of 68.0 microM and 1.25 nmol (mg protein)-1/30 s, respectively). The stimulation of disopyramide uptake by an outward H+ gradient in rat intestinal brush-border membrane was due to an interior negative H(+)-diffusion potential. A K(+)-diffusion potential (interior negative) enhanced disopyramide uptake. These results suggest that there are different mechanisms of disopyramide uptake for renal and intestinal brush-border membrane vesicles.

Animals↗

PubMed1993

Carbamazepine-induced hyponatremia in a patient with partial central diabetes insipidus.

A 51-year-old Japanese man was referred for the evaluation of persistent hyponatremia. The serum sodium level remained around 120 mmol/l despite mild water restriction. His past history included chronic alcoholism, myocardial infarction and lumbar disc herniation. Carbamazepine (200 mg, b.i.d.) has been used for more than 8 years for low back pain. Serum sodium returned to normal after carbamazepine was stopped, and rechallenge produced acute symptomatic hyponatremia (117 mmol/l) on day 2 after a total dose of 600 mg. Hepatic, renal and endocrine function were within normal limits, and the response to a water load (20 ml/kg) was also normal. Partial central diabetes insipidus was diagnosed by his response to water restriction and nasal desmopressin administration. Polyuria and hypernatremia were not evident in this case, probably due to a combination of low solute intake and low, but not deficient, levels of plasma ADH. This case demonstrates that carbamazepine may cause acute hyponatremia even in central diabetes insipidus, probably by sensitizing the distal renal tubules.

Carbamazepine↗

PubMed1993

[Pharmacokinetic and clinical studies of cefditoren pivoxil in the pediatric field. Pediatric Study Group of ME1207].

Cefditoren pivoxil (ME1207) in granules, a new oral cephalosporin, was pharmacokinetically and clinically evaluated in the pediatric field and the following results were obtained: 1. Pharmacokinetics In infants administered single oral doses of 3 mg (potency)/kg and 6 mg/kg, the Cmax was 1.54 +/- 0.68 and 2.85 +/- 1.03 micrograms/ml; Tmax, 2.27 +/- 1.08 and 2.06 +/- 1.16 hours; T 1/2, 2.22 +/- 1.95 and 1.68 +/- 0.66 hours; and AUC (0-infinity), 7.43 +/- 3.68 and 11.90 +/- 4.51 micrograms.hr/ml, respectively. These values have indicated that the drug has a dose-dependent pharmacokinetic behavior. Urinary concentrations peaked in 2-4 hours after administration. Urinary recovery rates in the first 8 hours were 19.4 +/- 6.6% at 3 mg/kg and 17.1 +/- 5.2% at 6 mg/kg. 2. Clinical results The clinical efficacy of the drug was evaluated in 445 patients with various infections. Cefditoren pivoxil was administered at daily doses of 9-18 mg/kg divided into 3 equal doses to most patients. Daily doses of > 7.5-10.5 mg/kg were given to 48.8% of the patients. The overall clinical efficacy rate was 97.3%, and this drug was effective in 97.5% of the 319 patients for whom the causative pathogens were identified and in 96.8% of the 126 patients with infections for whom the causative pathogens were unknown. The efficacy rate at daily doses of > 7.5-10.5 mg/kg was 97.2%, similar to that obtained at daily doses of > 10.5-19.5 mg/kg (97.0%). The bacteriological eradication rate was 90.4%. The efficacy and eradication rates for 66 patients who had not responded to previous chemotherapy were 95.5% (63/66) and 89.4%, respectively. Side effects occurred in 19 (4.2%) of 456 patients subjected to safety analyses. The primary side effect was diarrhea but no serious side effects were noted. As abnormal laboratory test results, moderate increases of the eosinophils and platelets counts as well as moderate elevations of the transaminases were observed. These abnormalities are also seen with other cephems and to a similar extent. No particular and serious problems were associated with administration of this drug. Based on the above results, cefditoren pivoxil is considered to be very useful at a dose level of 3 mg/kg t.i.d. against most infections encountered in the pediatric field.

Administration, Oral↗

PubMed1992

Carrier-mediated transport system for choline and its related quaternary ammonium compounds on rat intestinal brush-border membrane.

The characteristics of the intestinal transport system for choline were investigated using isolated brush-border membrane vesicles from rat small intestine. In spite of the diminutive lipid solubility, the uptake of choline by membrane vesicles reflected smooth permeation into intravesicular space rather than the binding to the membrane surface. Physiological conditions, present in the intact intestine, such as an inward-directed Na+ or H+ gradient and inside negative membrane potentials, didn't directly involve in choline transport across the brush-border membrane. Moreover, an outward-directed H+ gradient had no significant effect on the time course of choline transport. However, in the absence of a driving-force, the initial uptake of choline exhibited a saturable manner. A kinetic analysis of the initial uptake rate gave an apparent Km of 159 microM. Furthermore, unlabeled choline caused both cis-inhibition and trans-stimulation for labeled choline transport, suggesting the existence of a carrier-mediated transport system for choline, classified as so-called 'facilitated diffusion'. Since tetramethylammonium, acetylcholine, and N1-methylnicotinamide caused both cis-inhibition and trans-stimulation, they appear to be accepted as the substrate of choline carrier. On the other hand, quaternary ammonium compounds (QACs) such as those which possessed hydrophobic parts in their molecules exhibited only cis-inhibition. They also inhibited Na(+)-dependent D-glucose transport, indicating that they influenced various carrier-mediated transport systems non-specifically due to interaction with the membrane. These findings strongly suggest that the choline transport system on the brush-border membrane of rat intestine recognizes only small molecular QACs as its substrate.

Animals↗

PubMed1992

Membrane-potential-dependent uptake of tryptamine by rat intestinal brush-border membrane vesicles.

The effect of membrane potential on the uptake of tryptamine, an organic cation, by rat intestinal brush-border membrane vesicles was studied. In the presence of an outwardly directed H(+)-gradient, the initial uptake of tryptamine was stimulated remarkably and the overshoot phenomenon was observed. In contrast, the uptake was depressed by an inwardly-directed H(+)-gradient. The effect of H(+)-gradient on the uptake of tryptamine was maintained in the presence of FCCP, whereas it vanished when voltage-clamped vesicles were used. Moreover, the uptake of tryptamine was linearly augmented with increase of the valinomycin-induced inside-negative K+ diffusion potential. These results suggest that tryptamine is taken up into intestinal brush-border membrane vesicles depends upon the ionic diffusion potential. The effect of several indole derivatives and amine compounds on the uptake of tryptamine was also examined. The uptake of tryptamine was inhibited by all amine compounds used, but anionic and zwitterionic compounds had no effect, suggesting that these amines interact on brush-border membrane and cause an inhibitory effect.

Amines↗