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Biomedical subjects

S Shintani

Publications and source records attributed to S Shintani.

At least 145 records · Page 8Linked to original sources
PubMed1985

General pharmacological properties of cilostazol, a new antithrombotic drug. Part II: Effect on the peripheral organs.

The pharmacological effects of the new antithrombotic drug, cilostazol (6-(4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4-dihydro-2(1H)-qui nolinone, OPC-13013) on the peripheral nervous system and miscellaneous organs were studied. Cilostazol produced a very slight increase in beating rate of the isolated atrium and a very slight increase in contraction of the papillary muscle of guinea pigs induced by cilostazol compared with that of isoproterenol (isoprenaline). The beating rate increasing effect was not antagonized by propranolol and it augmented isoproterenol's effect. When administered intravenously in anesthetized dogs, cilostazol increased blood flow in the coronary, internal carotid, vertebral and femoral arteries and transiently decreased blood flow in the renal and superior mesenteric arteries probably because of blood pressure fall. In anesthetized dogs, cilostazol decreased blood pressure by reducing the resistance in the peripheral blood vessels. An increase in heart rate, cardiac contractile force, myocardial oxygen consumption and respiration rate were also observed. In conscious rats, the drug increased heart rate. Cilostazol produced a slight relaxation of the smooth muscle of all organs except for blood vessels and slightly inhibited spontaneous motility of the isolated uterus of pregnant rats, the isolated ileum of rabbits and the ileum of rats in situ. It was considered that cilostazol had no specific effects against norepinephrine, serotonin, acetylcholine or histamine based on the results that the drug was only slightly antagonistic against the contraction of rabbit aorta induced by norepinephrine and serotonin, the contraction of isolated guinea-pig ileum induced by acetylcholine, histamine and barium chloride and the contraction of the isolated uterus of non-pregnant rats induced by oxytocin. The drug had little effect on the contraction of the nictitating membrane induced by stimulation of the preganglionic sympathetic nerve in the cat. These results suggest that cilostazol had little effect on the autonomic nervous system. Cilostazol slightly inhibited edema induced by carrageenin, but showed no diuretic effect and had little effect on neuromuscular transmission or the secretion of gastric juice, bile and pancreatic juice, and therefore it was considered to have no appreciable effect on the peripheral nervous system or organs except for its vasodilating and cardiac effects.

Anesthetics, Local↗
PubMed1985

General pharmacological properties of cilostazol, a new antithrombotic drug. Part I: Effects on the central nervous system.

The pharmacological effects of the new platelet aggregation inhibitor cilostazol (6-(4-(1-cyclohexyl-1 H-tetrazol-5-yl)butoxy]-3,4-dihydro-2(1H)-quinolinone, OPC-13013) on the central nervous system were studied. Cilostazol had little effect on the general behavior of mice up to a dose of 1000 mg/kg p.o. and caused disappearance of pinna reflex, alertness and startle response and slight ptosis in only one of 6 rats at a dose of 1000 mg/kg p.o. Cilostazol had little effect on spontaneous movement and motor coordination in mice and did not potentiate hexobarbital-induced hypnosis, antagonize methamphetamine-induced hypermotor activity, cause muscle relaxation or have an anticonvulsant effect. Cilostazol did not affect normal body temperature but slightly antagonized reserpine-induced hypothermia at 300 mg/kg p.o. in mice. Cilostazol did not show an analgesic effect by Haffner's method, but it did slightly inhibit acetic acid-induced writhing at doses higher than 300 mg/kg p.o. in mice. The inhibitory effect was considered to be due to its peripheral effect. Cilostazol had little effect on discriminated avoidance response in rats, EEG arousal response in rabbits or spinal reflex in cats. However, it did slightly increase the slow wave until about 2 h after administration at 1000 mg/kg p.o., but the slow-wave sleep period did not tend to persist for a long period. These results suggest that cilostazol had little effect on the central nervous system.

Analgesics↗
PubMed1982

[Pharmacological properties of buprenorphine, a new analgesic agent. Part II. (author's transl)].

Pharmacological properties of buprenorphine were compared with those of morphine and pentazocine. Buprenorphine scarcely showed any effects on spontaneous EEGs and sleep-wakefulness cycles. Buprenorphine tended to depress the recruiting and augmenting responses and the spindle burst, and it also inhibited the hypothalamic arousal response. Buprenorphine had weaker emetic action than morphine and protected against apomorphine-induced emesis in the same manner as morphine. Buprenorphine scarcely affected respirations, blood pressure, heart rate, blood flow, ECG, cardiac contractile force, cornary flow, and intracranial pressure. However, morphine and pentazocine caused depressed respiration, decreased blood pressure, increased blood flow and cardiac contractile force, and elevated intracranial pressure. Buprenorphine, morphine, and pentazocine did not affect bile secretion, but produced contraction of the sphincter of Oddi. Buprenorphine had very little effect on renal function, but morphine and pentazocine reduced this function to depress urine flow. Buprenorphine and morphine inhibited carrageenin-induced edema. Buprenorphine had no effect on blood histamine level, but morphine increased the concentration of histamine. These results indicate that buprenorphine has little effect on the central nervous system, respiratory and cardiovascular system, and renal function.

Analgesics, Opioid↗
PubMed1982

[Interactions between buprenorphine, narcotic analgesic, and centrally acting drugs in prolongation of halothane-induced sleeping and analgesia (author's transl)].

Interactions between buprenorphine, narcotic analgesic, and centrally acting drugs were studied in prolongation of halothane-induced sleeping and analgesia using the D'Amour-Smith method in mice, and the effect of buprenorphine on monoamine metabolism was studied in rat brain. Diazepam and chlorpromazine prolonged the halothane-induced sleeping time dose-dependently. Buprenorphine (0.01, 0.1, and 1 mg/kg s.c.) inhibited the effect of diazepam, but not that of chlorpromazine. Pentazocine and naloxone also inhibited the effect of diazepam, but morphine did not. It is suggested that the inhibitory effect of buprenorphine on prolongation of halothane-induced sleeping time by diazepam is due to its opiate antagonistic property. Since narcotic antagonists inhibited the effect of diazepam, the endogenous opiate system seems to be involved in this effect. Diazepam or droperidol had no effect on the analgesia of buprenorphine, morphine, and pentazocine. Buprenorphine analgesia was inhibited by reserpine and p-chlorophenylalanine, potentiated by 5-hydroxytryptophan, and not affected by alpha-methyl-p-tyrosine or 3,4-dihydroxyphenylalanine. These results suggest that the serotonergic system plays a modulating role in buprenorphine analgesia. Imipramine and nialamide inhibited buprenorphine analgesia in the test at low stimulus intensity, but potentiated at high stimulus intensity. Buprenorphine (0.1, 1 and 10 mg/kg s.c.) increased the dopamine metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, in various brain areas and the serotonin metabolite, 5-hydroxyindoleacetic acid, in midbrain.

Analgesia↗
PubMed1982

[Analgesic and narcotic antagonist effects of buprenorphine (author's transl)].

Pharmacological properties of buprenorphine were studied in comparison with those of morphine and pentazocine. Buprenorphine was more potent than morphine and pentazocine in analgesic tests, using chemical, thermal, pressure, and electrical stimulation as the nociceptive stimuli. Buprenorphine exhibited analgesic activity in the D' Amour-Smith's test at high stimulus intensity and in the Haffner's test, while pentazocine exhibited little or no analgesic action in these tests. Buprenorphine showed a bell-shaped dose-response curve in the mouse D'Amour-Smith's test at high stimulus intensity. Analgesic action of buprenorphine was antagonized by naloxone administered before buprenorphine, but not antagonized by naloxone administered after buprenorphine. Duration of the analgesic action of buprenorphine was longer than those of morphine and pentazocine. Buprenorphine decreased the amplitudes of evoked potentials which were recorded from the nucleus ventralis posteromedialis, nucleus centralis lateralis, and periaquaductal central gray. As a naloxone antagonist, Buprenorphine was equivalent or less potent than naloxone and more potent than pentazocine. Tolerance developed to the analgesic activity of buprenorphine, but development of tolerance to buprenorphine was less than that of tolerance to morphine. It was concluded that buprenorphine may be a useful analgesic drug because of its high intrinsic activity and long duration of action.

Analgesics↗
PubMed1980

Determination of ethambutol in plasma using selected ion monitoring.

The determination of ethambutol in plasma is described. Using ethambutol-d4 as an internal standard, ethambutol and the internal standard were extracted with chloroform under alkaline conditions, and converted into their trifluoroacetyl derivatives with trifluoroacetic anhydride in benzene-pyridine (4:1). Selected ion monitoring was carried out by monitoring the peaks at m/z 294 and 296 corresponding to the fragment ion [M/2]+ of the derivatives. Ethambutol was determined by use of the peak height ratio of the peak at m/z 294 against that at m/z 296. The method was utilized for studying the bioavailability and pharmacokinetics of the drug.

Animals↗
PubMed1980

Sensitive and selective method for the determination of chlormezanone in plasma by electron-capture gas chromatography.

A sensitive and selective determination method of chlormezanone in plasma has been divised. Chlormezanone in plasma was extracted with toluene at pH 4.5, and converted into p-chlorobenzaldehyde in 0.1 N NaOH. Using p-bromobenzaldehyde as an internal standard, the hydrolysis product and the internal standard were extracted with n-hexane, and the extract was concentrated in vacuo in the presence of isoamyl alcohol to prepare the sample solution. The sample solution was submitted to electron-capture gas chromatography. Chlormezanone was determined by use of the peak height ratio of p-chlorobenzaldehyde against the internal standard. The method was utilized successfully for pharmacokinetic studies of chlormezanone in plasma.

Benzaldehydes↗
PubMed1980

Analysis of drugs by pyrolysis. II--An improved method for the determination of carpronium chloride in plasma by selected ion monitoring.

A sensitive and specific method has been devised for the determination of carpronium chloride, a parasympathomimetic agent, in plasma. The method is based on selected ion monitoring combined with the pyrolysis reaction of (3-isopropoxycarbopropyl)trimethylammonium chloride derived by transesterification of the drug. Carpronium chloride-[2H9] is used as an internal standard. The drug and the internal standard are separated from deproteinized plasma by ion pair extraction, and converted into isopropyl ester derivatives. The derivatives are pyrolysed to produce the respective isopropyl N,N-dimethyl-gamma-aminobutyrates available for selected ion monitoring. Measurement is carried out in the electron impact mode by monitoring the fragment ion [M-OC3H7]+ (m/z 114, 120). The method is applicable to 5 ng ml-1 plasma with about 10% coefficient of variation, and has been utilized successfully for the pharmacokinetics of carpronium chloride in man.

Animals↗
PubMed1979

[Pharmacological properties of procaterol, a newly synthetized, specific beta 2-adrenoceptor stimulant. Part I. Effects on the CNS (author's transl)].

Effects of procaterol (PRO) on the CNS were investigated in comparison with those of salbutamol (SAL) and isoproterenol (ISO). PRO, 15 to 50 mg/kg given subcutaneously suppressed spontaneous movement in mice, rats and rabbits and with a large dose, 1000 mg/kg, the animals became quiet and immobile. In dogs, PRO produced similar symptoms and in addition, there was nausea and vomiting. The animals recovered within 3--8 hours. ID50's in depressing spontaneous movement were 20.2 and 245 mg/kg for PRO, 51.1 and 133 mg/kg for SAL and 2.37 and 143 mg/kg for ISO, respectively, both by the subcutaneous and oral routes of administration. Methamphetamine induced increase in motility and fighting behavior was also suppressed by PRO when similar doses were given. PRO had no effect on coordinating movement, halothane anesthesia, drug and electric stimulation induced convulsions and body temperature, and there was no muscle relaxant action. However, PRO in large doses prolonged sleeping time with hexobarbital. The analgesic effect of PRO was not observed with Haffner's and Landall Selitto's methods but acetic acid induced writhing was suppressed by PRO. PRO had little effect on spontaneous EEGs either cortical or from deep structures, and EEG arousal responses. The effects of PRO on the CNS were slight and nonspecific, and similar to those of SAL and ISO.

Adrenergic beta-Agonists↗
PubMed1979

[Pharmacological properties of procaterol, a newly synthesized, specific beta 2-adrenoceptor stimulant. Part II. Effects on the peripheral organs (author's transl)].

Pharmacological properties of procaterol (PRO) in the peripheral organs were examined in comparison with those of sulbutamol (SAL) and isoproterenol (ISO). PRO slightly enhanced twitch tension of the tibialis anterior muscle but affected little the mono- and poly-synaptic spinal reflexes and ganglionic transmission. PRO depressed spontaneous contractions of the isolated ileum, non-pregnant and pregnant uterus and also the gastrointestinal and uterine movements in vivo. PRO prolonged the time of peroral charcoal transport in the intestine. Potencies of PRO in producing these effects were between those of ISO and SAL except those on the uterus in which PRO was more potent than ISO and SAL. Pro depressed gastric and bile secretion but had no effect on pancreatic secretion. ISO, PRO and SAL reduced resistance of the common carotid, femoral and renal arteries and the relative potencies of PRO and SAL to ISO were significantly less in the renal artery than in the other arteries. In accelerating heart rate in conscious rats and dogs, PRO (p.o. or s.c.) was almost equipotent to SAL. Urine flow, GFR, RPF, free water and osmolar clearance and also excretion of electrolytes were reduced by PRO with the concomitant fall of systemic blood pressure. PRO has no effect on blood coagulation and hemolysis but inhibited carrageenin edema and an increase in permeability of blood vessels induced by acetic acid. PRO had no alpha-adrenolytic, cholinolytic and anti-histaminic effects.

Adrenergic beta-Agonists↗
PubMed1975

[Effects of 5-(3-tert-butylamino-2-hydroxy) propoxy-3,4-dihydrocarbostyril hydrochloride(OPC-1085) on coronary circulation and myocardial metabolism].

Effects of a new beta-adrenergic blocking agent, 5-(3-tert-butylamino-2-hydroxy) propoxy-3,4-dihydrocarbostyril hydrochloride (OPC-1085), on the coronary circulation and myocardial metabolism were investigated in anesthetized open-chest dogs and isolated perfused dog hearts. In anesthetized open-chest dogs, OPC-1085 antagonized the responses to isoproterenol of heart rate, Vmax, mean blood pressure, myocardial oxygen consumption, coronary blood flow and redox potential. The antagonistic potency of OPC-1085 was stronger than propranolol. OPC-1085 3 to 30 mug/kg caused appreciable decreases, but in doses of 100 to 1,000 mug/kg caused increases in heart rate and Vmax. The effect of OPC-1085 on max dp/dt was similar to that on Vmax. However, propranolol 3 to 3,000 mu-g/kg caused only decreases in heart rate, Vmax and max dp/dt. OPC-1085 3,10 mu-g/kg while propranolol 30, 100 mu-g/kg caused a fall in myocardial oxygen consumption and coronary blood flow. In isolated perfused hearts, intracoronary injection of OPC-1085 0.1 mg almost completely suppressed isoproterenol-induced augmentation of heart rate, myocardial contractile force and coronary blood flow and reduction of redox potential. OPC-1085 0.1 mg caused slight increases in heart rate, myocardial contractile force and myocardial oxygen consumption. It is concluded that OPC-1085 is a more potent beta-adrenergic blocking agent than propranolol and possesses a weak negative inotropic effect in doses of 3 to 30 mu-g/kg and a intrinsic sympathomimetic activity in doses of 100 to 1,000 mu-g/kg.

Animals↗
PubMedDate not supplied

Repeat MRI in acute rhabdomyolysis: correlation with clinicopathological findings.

OBJECTIVE: Four cases of acute rhabdomyolysis are presented and the correlation between clinicopathological and MR findings is discussed. MATERIALS AND METHODS: The cases include carnitine palmitoyltransferase I deficiency presenting as compartment syndrome, acute polymyositis, acute myositis associated with Epstein-Barr virus infection, and glycyrrhizin- and diuretic-induced hypokalemic myopathy. RESULTS: The T2-weighted MR images revealed high intensity lesions in the affected muscle groups. The lesions seen on MR correlated precisely with the symptoms and neurological deficits of the patients. Repeat MR studies showed that the high intensity lesions seen on T2-weighted MR images resolved in parallel with the clinical course. CONCLUSION: This reversibility of the MR findings suggests that the high intensity lesions do not reflect permanent myopathic changes, but probably represent transient edema in the acute phase of rhabdomyolysis.

Acute Disease↗
PubMedDate not supplied

Antiarrhythmic properties of 5-(3-tert-butylamino-2-hydroxy)propoxy-3,4-dihydrocarbostyril hydrochloride (OPC-1085), a newly synthesized, potent beta-adrenoreceptor antagonist.

1. The antiarrhythmic properties of 5-(3-tert-butylamino-2-hydroxy)propoxy-3,4-dihydrocarbostyril hydrochloride (opc-1085) were compared with those of propranolol and pindolol using various kinds of preparations for experimental arrhythmia in dogs. 2. Although OPC-1085 was the most potent drug to antagonize adrenaline-induced arrhythmia in animals anaesthetized with either pentobarbitone sodium or halothane, it was scarcely effective on ouabain-induced arrhythmia in pentobarbitone sodium anaesthetized animals. 3. When these compounds were administered intravenously to conscious dogs 24 h after two-stage ligation of the anterior descending artery, ectopic ventricular beats of coronary ligation-induced arrhythmia were reduced while regular sinus beats were simultaneously increased. 4. OPC-1085 was very effective on aconitine-induced arrhythmia in dogs anaesthetized with pentobarbitone sodium. The effective dose was similar to that of propranolol but about fifteen times less than that of pindolol. 5. It is concluded that different potencies among these beta-adrenoreceptor antagonists against various kinds of experimental arrhythmias cannot be simply deduced from any one of the following properties; beta-adrenoreceptor antagonism, intrinsic myocardial stimulation, local anaesthetic and so-called quinidine-like effects.

Aconitine↗