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Biomedical subjects

K Takao

Publications and source records attributed to K Takao.

At least 55 records · Page 3Linked to original sources
PubMed1992

Role of the central serotonergic system in the anticonflict effect of d-AP159.

d-AP159 is a d-optical isomer, and in rats it has a high affinity for 5-hydroxytryptamine1A (5-HT1A) receptors and potent anticonflict activity, equal to that of buspirone. The anticonflict effects of d-AP159 and buspirone were investigated in animals in which lesions of the serotonergic neurons were caused by intradorsal raphe (d-RA) injection of the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT). The anticonflict effect of buspirone, but not that of d-AP159, was attenuated in 5-HT neuron-lesioned rats. The anticonflict effect of d-AP159 injected into various brain sites was also studied. d-AP159 and buspirone microinjected into the d-RA caused significant anticonflict activity in rats. There was a significant anticonflict effect of d-AP159 injected into the amygdala centralis (ACE), but not the dorsal hippocampus (d-HC). The anticonflict effect of d-AP159 injected into the d-RA was antagonized by systemic administration of (-)propranolol but not Ro 15-1788. This effect of d-AP159 injected into the ACE was antagonized by systematic administration of Ro 15-1788 but not (-)propranolol. These results suggest that the d-RA and the ACE play important roles in the anticonflict effects of d-AP159 but that the mechanisms by which this drug acts at these sites are different.

5,7-Dihydroxytryptamine↗
PubMed1991

Pharmacological profile of a potential anxiolytic: AP159, a new benzothieno-pyridine derivative.

AP159 [N-cyclohexyl-1,2,3,4-tetrahydrobenzo(b)thieno(2,3c)pyridine]-3- carboamide,hydrochloride) showed clear anti-conflict activity in rats in the absence of effects on muscle relaxation, potentiation of anesthesia (in mice) or anticonvulsant activity (in mice). This anti-conflict effect was antagonized by treatment with Ro15-1788. By contrast with the deficits produced by diazepam, AP159 did not impair passive avoidance. The latter drug also improved scopolamine-induced amnesia in the same task. AP159 did not inhibit 3H-flunitrazepam binding, but potently inhibited 3H-8OH-DPAT binding. This compound increased serotonin and 5HIAA content of the midbrain raphe nuclei and of the amygdala centralis. AP159 has been shown to be a novel non-BZP anxiolytic agent with no side effects in laboratory animals; it could be a clinically effective anxiolytic agent.

Aggression↗
PubMed1990

Potent anticonflict activity and lessening of memory impairment with a series of novel [1]benzothieno[2,3-c]pyridines and 1,2,3,4-tetrahydro[1]benzothieno[2,3-c]pyridines.

[1]Benzothieno[2,3-c]pyridines (10a-c, 11, 12a-t, and 13a,b) and 1,2,3,4-tetrahydro[1]benzothieno[2,3-c]pyridines (3a-c, 7, 8a-c, and 9) were synthesized. The compounds are bioisosteres of beta-carbolines and 1,2,3,4-tetrahydro-beta-carbolines where the indole nitrogen is replaced by sulfur. Their pharmacological activity was evaluated in a water lick conflict test in rats and a passive avoidance test in mice. In the 1,2,3,4-tetrahydro[1]benzothieno[2,3-c]pyridine series, the presence of ethyl ester (3b) or cyclohexyl carboxamide (7) groups at C-3 conferred good anticonflict activity and lessening of memory impairment, while N-acylation of 3b abolished activity. In the [1]benzothieno(2,3-c]pyridine series, the aminoethyl carboxamide (12a) group at C-3 also conferred activity, but other amides studied were not active. The most potent compounds (3b, 7, and 12a) were also administered orally and had potent anticonflict and antiscopolamine amnesia-reversal activity. These compounds did not bind to the BZP receptor in spite of having structures similar to those of beta-carbolines. Compound 7 bound strongly to 5-HT1A receptors and would be expected to be a novel anxiolytic.

Animals↗
PubMed1990

beta-CCM inhibits muricide induced by olfactory bulbectomy in rats.

Intravenous administration of beta-CCM (methyl-beta-carboline-3-carboxylate) at doses ranging from 0.3 to 10 mg/kg dose-dependently inhibited muricide in olfactory bulbectomized rats. beta-CCM elicited a decrease of locomotor activity at doses ranging from 0.3 to 3 mg/kg, and it impaired rotarod performance at doses of 1 and 3 mg/kg. The inhibition of muricide induced by beta-CCM was antagonized by intraperitoneal administration of Ro15-1788 at 10 mg/kg or diazepam at 3 mg/kg. However, the hypolocomotor activity and impairment of rotarod performance induced by beta-CCM were not antagonized by diazepam at 3 mg/kg. These results indicated that beta-CCM exerts an inhibitory effect on muricide through benzodiazepine receptors and this inhibitory effect was not solely caused by its sedative or motor incordinating activity at the dose ranges used in this study.

Aggression↗
PubMed1988

Anti-serotonin action in combination with noradrenaline-stimulating action is important for inhibiting muricide in midbrain raphe-lesioned rats.

The present study was designed to examine the possible involvement of both an anti-serotonin action and a catecholamine-stimulating action in the mechanism of the inhibition of the muricide in rats with lesions of the midbrain raphe. Serotonin antagonists, such as cyproheptadine (10 mg/kg), cinanserin (10 mg/kg) and pirenperone (1 mg/kg), given alone showed little suppression of muricide in rats with raphe lesions, although the first two drugs were inhibitory at very large doses. Methamphetamine showed no inhibition of muricide at 0.32 mg/kg (i.p.), but exerted a marked inhibition of muricide when combined with the above serotonin antagonists. In addition, the dose-response curve for cyproheptadine and cinanserin was shifted markedly to the left when combined with L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) (100 mg/kg i.p.), but not with lisuride (0.32 mg/kg i.p.). Similarly, pirenperone produced a marked inhibition of muricide at doses of 0.32-1.8 mg/kg (i.p.) when combined with L-threo-DOPS, but not when combined with lisuride. These results suggest that the combination of an anti-serotonin action with noradrenergic activation is important for inhibiting muricide, at least in rats with raphe lesions. A similar mechanism also seems to be valid for the anti-muricidal effect of antidepressant drugs.

Aggression↗
PubMed1986

[Electroencephalographic effects of 450191-S and its metabolites in rabbits with chronic electrode implants].

Electroencephalographic (EEG) effects of 450191-S and its metabolites were investigated in unanesthetized rabbits with chronic electrode implants, and they were compared with those of nitrazepam and estazolam. 450191-S at doses of 0.1-0.5 mg/kg, i.v., induced a drowsy pattern of spontaneous EEG: high voltage slow waves and spindle bursts increased in the cortex and amygdala, while the hippocampal theta rhythm was desynchronized. In addition, low voltage fast waves appeared particularly in the cortical EEG. The EEG arousal response to auditory stimulation and to electric stimulation of the mesencephalic reticular formation, posterior hypothalamus and centromedian thalamus was markedly suppressed by 450191-S. The photic driving response elicited by a flash light in the visual cortex was significantly suppressed by 450191-S. 450191-S showed no significant effect on the recruiting response. The EEG effects of nitrazepam were qualitatively similar but less potent and shorter in duration of action than those of 450191-S. The effects of estazolam were approximately as potent as those of 450191-S, but its duration of action was much shorter than that of 450191-S. 450191-S was more potent than nitrazepam and approximately equipotent to estazolam in suppressing hippocampal and amygdaloid after-discharges. The EEG effects of M-1 and M-2 were similar to those of 450191-S in both qualitative and quantitative aspects. The effects of M-A were quantitatively similar but less potent and shorter in duration of action than those of 450191-S.

Animals↗
PubMed1986

[Efficacy of extrapleural internal mammary node dissection in breast cancer].

The results of extended radical mastectomy for breast cancer in 180 randomized patients treated at this department between 1965 and 1984 are reported. About 18% of the women with breast cancer had internal mammary lymph node metastasis. The incidence of metastasis in internal mammary lymph nodes increased from 9.5% when the tumor was locate in the outer half to 24.7% when it was in the center or inner half. The increase in the number of axillary lymph node metastasis was correlated with the increase in the incidence of internal mammary lymph node metastasis. The five-year survival rate of patients with no internal mammary lymph node involvement was better than that of involvement (81% versus 47%). But when the internal mammary nodes alone were involved without axillary lymph node metastasis, 83% of the patients survived for five years.

Adult↗
PubMed1984

An economic "power supply" using a diode for agarose and polyacrylamide gel electrophoresis.

Gel electrophoresis using agarose and polyacrylamide is a technique widely used for the separation of DNA and protein of various molecular sizes. This type of electrophoresis involves use of a rather expensive dc power supply composed of a complicated circuit. A simple circuit consisting of a single diode was designed, which can be used as a substitute for the conventional power supply. There are no appreciable differences in the so-obtained electrophoretic patterns. This simple, economic system is expected to be applied for use in laboratory, industrial, educational, and clinical facilities.

DNA↗