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Biomedical subjects

S Tachikawa

Publications and source records attributed to S Tachikawa.

At least 73 records · Page 4Linked to original sources
PubMed1984

New sulfamoylphenethylamines, potent alpha 1-adrenoceptor antagonists.

The (+)-isomer of amosulalol, a combined alpha- and beta-adrenoceptor antagonist, was one log unit order more potent and less potent than the (-)-isomer in blocking alpha 1- and beta 1-adrenoceptors, respectively, in anaesthetized rats. Nine newly synthesized desoxy compounds derived from amosulalol and its analogues were found to possess potent alpha 1-adrenoceptor blocking activity and to be practically devoid of beta 1-adrenoceptor blocking activity. Among the desoxy derivatives, YM-12617 was more potent than prazosin in blocking alpha 1-adrenoceptors in anaesthetized rats and in reducing blood pressure, total peripheral resistance and left ventricular work in anaesthetized dogs.

Adrenergic alpha-Antagonists↗
PubMed1984

[Bronchial asthma due to inhaled chloroplatinate].

Platinum and its compounds have characteristics that make them excellent oxygen sensors, and in recent years they have come to be used in large amounts in the manufacture of internal combustion engines. Recently, there have been detected among workers engaged in making platinum oxygen sensors, dermatitis and bronchial asthma which appear to be ascribable to exposure to chloroplatinate. This is a study of their etiology from the viewpoint of industrial hygiene and clinical medicine. The results obtained are as follows: Platinum-induced allergic disorders developed in a worker who applies about 50% chloroplatinate to zirconia porcelain. Although the concentration of platinum in the air was 2 microgram/m3 or less as determined by ACGIH, the worker was directly exposed to the dried powder of ammonium chloroplatinate with relatively high concentration; while the exposure was intermittent and topical, it resulted in aspiration of the powder. Bronchial asthma observed in 2 of 16 workers (12.5%) was reactive in a skin drop test with 1% chloroplatinate, and typical bronchial asthma was induced in an environmental provocation test carried out in a room where platinum sensors are made. Parameters obtained from periphero-hematological and immuno-serological tests were within the normal range. The main symptoms revealed by physical examination of workers exposed to chloroplatinate contact dermatitis in 11 (78.6%), pharyngeal irritation in 6 (42.9%), nasal obstruction in 2 (14.3%), frequent sneezing, coughing, and sputum in one each.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Effects of formoterol (BD 40A), a beta-adrenoceptor stimulant, on isolated guinea-pig lung parenchymal strips and antigen-induced SRS-A release in rats.

Formoterol was evaluated for its inhibitory effects on tissue tonus of the isolated guinea-pig lung parenchymal (peripheral airways) and tracheal (central airways) strips and on antigen-induced release of slow reactive substance of anaphylaxis (SRS-A) in the rat. Relaxant effects of formoterol in both parenchymal and tracheal strips were dose-dependent and were of similar potency. Formoterol was 44 and 100 times more potent than isoproterenol and salbutamol, respectively, in relaxing the parenchymal preparation. Propranolol, butoxamine and atenolol antagonized the relaxation of the parenchymal strips by formoterol in this order of decreasing potency; their slopes of regression line of the Schild plots were 0.809, 0.975 and 0.676, respectively. The inhibitory effect of intraperitoneally administered formoterol on (mouse) IgE-mediated SRS-A release in rat passive peritoneal anaphylaxis was 40 and 12200 times, respectively, more potent than those of salbutamol and disodium cromoglycate (DSCG). This action was antagonized by pretreatment with propranolol. In contrast to DSCG which dose-dependently inhibited histamine release, neither formoterol nor salbutamol was effective in inhibiting the release. The results indicate that formoterol potently relaxes the peripheral airways through stimulating the beta 2-adrenoceptors selectively as is the case in the central airways and that it significantly inhibits IgE-mediated SRS-A release through beta-adrenoceptor stimulation.

Adrenergic beta-Agonists↗
PubMed1983

[Studies on the effects of beryllium oxide in purity and fired temperature to the occurrence of chronic pulmonary berylliosis].

Among various beryllium (Be) compounds, beryllium oxide (BeO) has so far been noted as a causative substance which introduce chronic pulmonary berylliosis. In our study, chronic pulmonary berylliosis was experimentally evoked by using two species of BeO with individual purity and fired temperature (A group: 95.0% in purity, and 1,300 degrees C or above in fired temperature, B group: 99.9% in purity, and 800-1,000 degrees C in fired temperature), and demarcation of prepared Be concentration involving in the genesis of the disorder was examined. BeO with various concentrations ranging from 200 micrograms to 0.1 micrograms were mixed with 0.1% agar solution and infused into right thorax cavity of male guinea pig, following which variation of the body weight was checked and pulmonary histo-pathological findings, peripheral hematological tests, and sero-biochemical tests were carried out on a periodical basis at 8 weeks, 16 weeks, and 32 weeks. The results obtained are outlined herein. 1) Body weights of test animals in both A group and B group were significantly decreased as compared with that of the control. 2) Pulmonary histo-pathological findings revealed the genesis of epitheloid-cell granuloma in the lungs where non-infusion sides were included, which resembled to non-caseating granuloma in the human pulmonary berylliosis. 3) The frequency in the genesis of epithelaid-cell granuloma was 1/36 (2.8%) in A group and 4/35 (11.4%) in B group, granuloma formation being marked in the latter. 4) Examination of the frequency in terms of BeO dosages revealed no results suggesting the dose-response relationship between pulmonary granuloma formation and the dosage. 5) There were no changes worthy of note in peripheral hematological tests. 6) Sero-biochemical tests revealed that alkaline phosphatase value together with total protein in each was significantly decreased in B group at 32 weeks following the infusion.

Berylliosis↗
PubMed1983

Central alpha-adrenergic control of blood pressure. Effects of clonidine withdrawal.

Studies were undertaken to investigate the role of the CNS in withdrawal hypertension caused by abrupt cessation of long-term clonidine treatment. The studies were conducted on male wistar rats receiving clonidine, 100 micrograms/kg subcutaneously twice daily for seven days. Withdrawal hypertension occurred 16 to 18 hours following the last injection of clonidine. Pressor responses to posterior hypothalamic stimulation were significantly potentiated in the rats undergoing clonidine withdrawal, and the depressor response to a single injection of 10 micrograms of clonidine into the lateral cerebral ventricle was significantly attenuated in these animals. Studies on pithed rats demonstrated that destruction of the CNS eliminated the withdrawal hypertension. These data suggest that alpha-adrenoreceptors in the nucleus tractus solitarius play an important role in the normal maintenance of blood pressure, and a decrease in sensitivity of these receptors could result in the development of a hypertensive state.

Animals↗
PubMed1982

Pharmacological studies on a new benzamide derivative, YM-09151-2, with potential neuroleptic properties.

The electrophysiological properties and cataleptogenicity of YM-09151-2 (N-[(2RS, 3RS)-1-benzyl-2-methyl-3-pyrrolidinyl]-5-chloro-2-methoxy-4-methylaminobenzamide) were studied in the cat. This drug inhibited the EEG arousal response to electrical stimulation of the mesencephalic reticular formation with the same potency as that of haloperidol, whereas chlorpromazine revealed a more potent central depressant action. The duration of the afterdischarge induced by electrical stimulation of the amygdaloid nucleus was initially shortened and thereafter prolonged by both YM-09151-2 and haloperidol. However, YM-09151-2 was less effective than haloperidol and chlorpromazine in both augmenting the spindle bursts produced by electrical stimulation of the caudate nucleus and antagonizing the inhibitory effect of L-DOPA on the caudate spindle, indicating a smaller effect of YM-09151-2 on the extrapyramidal dopaminergic system than that of the two neuroleptic drugs. In fact, YM-09151-2 produced no cataleptic behaviour in the cat even at a dose of 5 mg/kg (s.c.), although haloperidol and chlorpromazine caused catalepsy in doses of 0.5 and 5 mg/kg (s.c.), respectively. Sulpiride, chemically related to YM-09151-2, showed much weaker central actions than YM-09151-2. The results indicate that a new benzamide, YM-09151-2, has a potent neuroleptic effect with a slight central depressant activity and that the cataleptogenicity of the compound is weaker than that of haloperidol and of chlorpromazine.

Amygdala↗
PubMed1982

Effects of porcine calcitonin on behavioral and electrophysiological responses elicited by electrical stimulation of the tooth pulp in rabbits.

Effects of porcine calcitonin on both behavioral and electrophysiological responses of rabbits to painful stimuli were examined. The behavioral pain response (licking reaction) to electrical stimulation of the tooth pulp was suppressed dose dependently by intracerebroventricular administration of calcitonin, 8 and 17 U/kg, but not by intravenous injection of 7.5-50 U/kg of the peptide. The duration of action of intracerebroventricular calcitonin was over 90 min. The EEG arousal response and the development of the long latency cortical potential evoked by electrical stimulation of the tooth pulp in gallamine-immobilized rabbits, were inhibited by intracerebroventricular calcitonin, 17 U/kg, for the period of over 90 min but not by the intravenous injection of 50 U/kg. Morphine, 2 mg/kg i.v., inhibited all of the responses for 30 min or longer. The EEG arousal response induced by sound stimulation was not affected by calcitonin or morphine. Naloxone (0.5 mg/kg i.v.), an opiate antagonist, showed no influence upon the inhibitory effects of calcitonin in licking reaction, EEG arousal response and evoked potential, though it completely antagonized the effects of morphine. The results suggest that the analgesic effect of intracerebroventricular porcine calcitonin can be attributed to blocking of pain pathways in the central nervous system in a manner distinct from the narcotic analgesic.

Animals↗
PubMed1981

[Central pharmacological effects of YPG-209 (16(S)-methyl-20-methoxy-prostaglandin E2) (author's transl)].

Central pharmacological effects of YPG-20 were examined in comparison with those of PGE2 (prostaglandin E2). Spontaneous motor activity and exploratory movement in mice were inhibited by oral administration of YPG-209 in a dose of 10 micrograms/kg. These inhibitions seemed to involve factors different from those related to the central nervous system, e.g. intestinal movement. Thiopental-induced sleeping time in mice was prolonged by oral administration of YPG-209 in a dose of 300 micrograms/kg. On the other hand, spontaneous EEG and EEG arousal response in gallamine-immobilized cats were not affected by intravenous administration of YPG-209 in a dose of 100 micrograms/kg. Mice taming effect, rota rod performance and drug- or electroshock-induced convulsions were not affected by oral administration of YPG-209 in a dose of 3 mg/kg. Methamphetamine-induced lethality in mice was inhibited by subcutaneous administration of YPG-209 in a dose of 5 mg/kg. Normal rectal temperature in mice was lowered by oral administration of YPG-209 in a dose of 5 mg/kg. Normal rectal temperature in mice was lowered by oral administration of YPG-209 in a dose of 100 micrograms/kg. The central pharmacological actions of PGE2 were qualitatively similar to those of YPG-209, but the potencies of central actions of PGE2 were less than those of YPG-209

Animals↗
PubMed1979

Lack of effect of levallorphan on analgesia induced by intraventricular application of porcine calcitonin in mice.

Intraventricular administration to mice porcine calcitonin (10 U/kg) as well as of morphine (3 microgram/kg) elevated the threshold pressure of stimuli applied to the base of the tail as assessed by squeaking, struggling or biting, all of which were regarded as manifestations of pain sensation in the animals. Pretreatment with an opiate antagonist, levallorphan (30 mg/kg i.p.) showed no influence upon the analgesic effect of calcitonin, though it completely antagonized the effect of morphine. The results suggested that a peptide hormone, calcitonin, exerted its analgesic action in a manner distinct from the narcotic analgesic.

Analgesics↗
PubMed1979

Pharmacological and biochemical studies on a new compound, 2-(7-indeyloxymethyl)morpholine hydrochloride (YM-08054-1), and its derivatives with potential antidepressant properties.

Antidepressant properties of a new indene derivative, YM-08054-1, and its related compounds were compared with those of tricyclic antidepressants and viloxazine. The potencies of YM-08054-1 to inhibit uptake of both 14C-norepinephrine (14C-NE) and 14C-5-hydroxytryptamine (14C-5-HT) by the rat brain synaptosomes were similar to those of amitriptyline and imipramine. Other indene derivatives with an N-alkylated morpholine ring were proved to have less effect on the uptake of either 5-HT or NE than was YM-08054-1. YM-08054-1 was the most potent among all of the tested antidepressants in the inhibition of reserpine-induced facilitation of convulsions as well as in the potentiation of reserpine-induced facilitation of convulsions as well as in the potentiation of 5-hydroxytryptophan (5-HTP)-induced syndromes in mice, though the inhibitory effect of this agent on reserpine-induced hypothermia was weaker than that of either amitriptyline or desipramine, suggesting relatively selective effects of YM-08054-1 upon 5-HT rather than NE uptake in vivo. Neither viloxazine nor iprindole potentiated the responses to 5-HTP. YM-08054-1 was devoid of peripheral anticholinergic activity and exhibited weak local anesthetic effect as well as low acute toxicity when compared with amitriptyline. The results indicate that YM-08054-1 has a novel profile as an antidepressant agent which is quite different from that of either viloxazine or tricyclic compounds.

Anesthetics, Local↗
PubMed1978

Effects of indenolol (YB-2), a new beta-adrenergic blocking agent, and its dextro isomer on the central nervous system of mice and rabbits.

Central depressant actions of a new beta-adrenergic blocking agent, indenolol (YB-2), and its dextro isomer were studied in mice and rabbits. d-Indenolol was less active than dl-indenolol in lowering of methamphetamine group toxicity and calming of fighting behavior, though muscle relaxant, hypolocomotive and anticonvulsant effects of d-indenolol were virtually equal to those of the racemate. dl-Propranolol showed a similar profile of central depressant actions to dl-indenolol, whereas dl-practolol revealed no significant central effects in mice. The dose-response relationship between beta-blocking and central effects in the same animal species suggested that both taming and anti-methamphetamine group toxicity effects of dl-indenolol s.c. do not directly relate to either the peripheral beta-blocking or the membrane stabilizing activity. Intravenous as well as intracerebroventricular administration of dl-indenolol resulted in suppression of pressor responses to the electrical stimulation of the brain stem of unanesthetized rabbits. Neither d-indenolol nor dl-practolol was effective against the pressor responses, suggesting that these two compounds acted on the CNS in a manner different from dl-indenolol even when intracerebroventricularly administered. A possible central beta-adrenergic blocking effect of dl-indenolol was discussed in the light of mechanisms of an antihypertensive action of this compound.

Adrenergic beta-Antagonists↗