[Prediction of resistance of depression to drug therapy by diagnostic scales].
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Biomedical subjects
Publications and source records attributed to Y Kudo.
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1. The role of Ca2+ in L-glutamate-induced depolarization was investigated in the isolated frog spinal cord. 2. The size of a depolarization induced by L-glutamate (3 mM) was inversely related to the extracellular Ca2+ concentration, but was reduced in a Ca2+-free medium containing EGTA (0.3 mM). 3. L-Glutamate caused a marked depolarization in both ventral and dorsal roots, even in a NaCl-deficient medium (Ca2+, 2.0 mM). The size of the depolarization was attenuated by a prolonged or repeated application of L-glutamate. Ca2+ can be replaced by Sr2+ or Mg2+. 4. Concanavalin A (1 microM) prevents the development of desensitization to L-glutamate. 5. Present results suggest that Ca2+ plays the role of a charge carrier for L-glutamate-induced depolarization and of a regulator of modulator for L-glutamate-receptor sensitivity. The roles are exaggerated in NaCl-free medium.
A double-blind study was conducted on triazolam, using nitrazepam and placebo as control compounds; statistically significant differences were demonstrated in favor of triazolam compared with placebo and with nitrazepam in many aspects of efficacy, but there was no significant difference between triazolam and nitrazepam in the incidence of concomitant symptoms and side effects. The fact that a certain quantity of triazolam is equivalent in strength to ten times that quantity of nitrazepam suggests the high potency of the former. These data indicate that triazolam is a valuable sleep inducer, with highly-rated efficacy and safety.
Ratios of cardiac to vascular beta-receptor blockade (C:V ratios) of atenolol and propranolol were determined in pentobarbital anesthetized spontaneously hypertensive (SHR) rats. These values and the cardiovascular responses to isoproterenol were compared with those of age-matched normotensive control (Donryu, DON) rats reported previously. Mean blood pressure (BP) and heart rate (HR) were recorded. Full dose-response curves for isoproterenol were constructed in BP and HR. In vivo pD2 values of isoproterenol (potencies), were not different between DON and SHR rats, although the maximal responses to isoproterenol (efficacy) were significantly suppressed in SHR rats. C:V ratios of atenolol and propranolol in SHR rats were 7.95 and 0.44, respectively. As the values in DON rats were 9.77 and 1.20, respectively, C:V ratios of atenolol and propranolol were decreased in SHR rats. Markedly decreased C:V ratios of propranolol in SHR rats may explain its relatively weak antihypertensive action.
Using the Coil Planet Centrifuge system, effects of single and repeated subcutaneous injections of p-nitrochlorobenzene [PNCB], aniline [AN] and phenylhydrazine [PH] on the osmotic fragility of red cell membrane in rabbits were studied. Methemoglobin [MHb] levels and appearance of Heinz bodies were also determined. In the single injection experiment, the osmotic fragility was increased immediately after the subcutaneous injections of PNCB [50 mg/kg, 100 mg/kg and 200 mg/kg], AN [50 mg/kg, 250 mg/kg and 500 mg/kg] and PH [25 mg/kg and 45 mg/kg]. The increased MHb levels were observed first, and secondly the maximum changes of the osmotic fragility and appearance of Heinz bodies were observed nearly simultaneouly after the injections of these three compounds. In the repeated injection experiment, hemolysis starting point was shifted toward higher osmotic pressure immediately after the injections of PNCB [5 mg/kg/day and 10 mg/kg/day], AN [20 mg/kg/day and 30 mg/kg/day] and PH [1 mg/kg/day and 3 mg/kg/day], while it was shifted toward lower osmotic pressure after the last doses of PNCB and PH. Hemolysis ending point was shifted toward higher osmotic pressure after the injections of PNCB [10 mg/kg/day] and AN, while it was shifted toward lower osmotic pressure after the injections of PNCB [5 mg/kg/day] and PH. The injection of PNCB induced continuously the increased MHb levels and appearance of Heinz bodies. The injection of PH induced the continuous appearance of Heinz bodies and the transiently increased MHb levels. Although the injection of AN induced the transiently increased MHb levels, there were no appearance of Heinz bodies. These findings show that the early and continuous changes in red cell membrane induced by these three compounds were able to be detected by the use of the Coil Planet Centrifuge system. The changes in red cell membrane induced by single and repeated injections of PH were able to be detected even when the increased MHb levels were not detected. Furthermore, the changes induced by the repeated injection of AN were able to be detected even when the increased MHb levels and the appearance of Heinz bodies were not detected. Thus, it seems likely that the Coil Planet Centrifuge method is useful to examine workers exposed to aromatic nitro and amino compounds.
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Anisatin depressed the conductance increase produced by GABA in a non-competitive manner and decreased the amplitude of the inhibitory junctional potentials. The presynaptic inhibition was depressed by anisatin in the similar concentrations to those of picrotoxin. The blockade of the presynaptic inhibition by anisatin was irreversible, whereas the effect of anisatin on postsynaptic inhibition subsided after prolonged washing of the preparation.
The neuropharmacological properties of anisatin were tested on the frog spinal cord and the crude synaptic membrane from rat brain. Anisatin (10(-5) M) reduced the amplitude of dorsal root potentials induced by stimulation of the adjacent dorsal root and presynaptic inhibition of the ventral root reflex. Anisatin shifted the dose-response curve for GABA-induced depolarization in the primary afferent terminal to the right and also reduced the maximum response to GABA. [3H]Muscimol binding to the crude synaptic membrane was not inhibited by anisatin. These results indicate that anisatin is a picrotoxin-like, non-competitive GABA-antagonist.
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We have devised a simple method to determine the ratios of cardiac to vascular beta-receptor blockage (C:V ratios) in normotensive rats anesthetized with pentobarbital, and applied it to six beta-adrenergic blocking drugs (beta-blockers). Mean blood pressure (BP) and heart rate (HR) were recorded. Isoproterenol (3 ng-100 microgram/kg, i.v.) was cumulatively injected before and after the intravenous administration of beta-blockers at two dose-levels. Thus shifts of the dose-response curves in BP and HR were observed. "In vivo pA2" values were calculated in molar doses per kg by Schild plots. The C:V ratio was calculated as antilogarithm of the difference of the mean in vivo pA2 value in HR from that in BP. Those of atenolol, bometolol, bunitrolol, pindolol, propranolol, and sotalol were 9.77, 8.13, 2.95, 1.38, 1.20, and 0.71, respectively.
Bometolol is a cardiospecific beta-adrenergic blocking drug. The effect on blood pressure was determined in hypertensive rats in acute and subchronic experiments. In acute experiment bometolol, 10-30 mg/kg, p.o., was given to spontaneously hypertensive rats; deoxycorticosterone and salt hypertensive rats; and two kidney, one clip hypertensive rats. Blood pressure was determined continuously for 8 h and after 24 h in unanesthetized condition. The blood pressure lowered by bometolol was dose-dependent in three types of hypertension. In subchronic experiment, bometolol at a dose of 10-30 mg/kg or 100-300 mg/kg, p.o., were given for 5 weeks to deoxycorticosterone and salt hypertensive rats; and two kidney, one clip hypertensive rats. Bometolol did not show antihypertensive effect in either type of hypertension, although bometolol decreased heart rate dose-dependently. Bometolol treatment at the above doses decreased plasma renin activity, heart and kidney weights, and incidence of vascular lesion in either hypertensive rat. Toxic symptom was seen 3 days after bometolol treatment of 300 mg/kg in deoxycorticosterone and salt hypertensive rats.
Lyoniol-A (2mg/kg, i.v.), a toxic component isolated from the Ericaceous tree, markedly caused the increase in rate of discharges from vagal afferent nerves in the rat. This agent also caused respiratory depression, hypotension and the relief of decerebrate rigidity. These effects of lyoniol-A on the respiration an the rigidity were absent under conditions of bilateral cervical vagotomy, and the hypotension was abolished by sectioning of both vagal and carotid sinus nerves. These results suggest that the excitation by lyoniol-A of the afferent activities reflexly produces respiratory depression, hypotension and the relief of decerebrate rigidity.
The present study was carried out to elucidate whether or whether not afloqualone has a hypnotic action because of its similarity in chemical structure to methaqualone. In the sleep-wakefulness cycles during the 8-hour observation period (9:00-17:00), afloqualone increased the percentages of resting (REST) and slow wave light sleep (SWLS) stages at a dose of 25 mg/kg (p.o.), producing a moderate muscle relaxation. Even at a dose of 50 mg/kg (p.o.) where a marked muscle relaxation was produced, afloqualone had no influence on the percentage of slow wave deep sleep (SWDS) stage, though it increased the percentages of SWLS and decreased the percentages of awake (AWK), REST and fast wave sleep (FWS) stages. On the other hand, tolperisone . HCl, chlormezanone, methaqualone and pentobarbital . Na, used as the reference drugs, all increased the percentage of SWDS stage, but either decreased or had no effect on the percentages of the other four stages at pharmacologically effective doses. From these results it was concluded that afloqualone seems to be devoid of a hypnotic action and has different effects on the sleep-wakefulness cycle than those of both the hypnotics and the other muscle relaxants used.