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Biomedical subjects

T Nabeshima

Publications and source records attributed to T Nabeshima.

At least 415 records · Page 23Linked to original sources
PubMed1981

[Pharmacological action of eptazocine (l-1,4-dimethyl-10-hydroxy-2,3,4,5,6,7-hexahydro-1,6-methano-1H-4-benzazonine). (I). Relationship between the analgesic action of eptazocine and brain catecholamine (author's transl)].

The relationship between the analgesic action of eptazocine and brain catecholamine was investigated by pharmacological and neurochemical methods in comparison with pentazocine (PZC) and morphine (MOR). The analgesic action of eptazocine as determined by the pressure method was decreased by pretreatment with 6-hydroxydopamine (6-OHDA) or disulifram. Eptazocine increased the norepinephrine (NE)level in the brain stem, but decreased the dopamine (DA) level in the cortex. Eptazocine decreased the rates of DA turnover in the cortex and the brain stem and NE turnover in the spinal cord. The analgesic action of PZC was decreased by alpha-methyl-rho-tyrosine ( alpha-MT), disulfiram, 6-OHDA, or reserpine. PZC decreased NE levels in the cortex and the brain stem, and DA level in the striatum. The turnover rates of NE in the brain stem and the spinal cord were increased by PZC. The analgesic action of MOR was potentiated by alpha-MT and attenuated by reserpine or 6-OHDA. MOR decreased NE and DA levels in the cortex and NE level in the brain stem, but increased DA level in the brain stem and NE level in the spinal cord. The turnover rates of NE in the cortex and the brain stem were increased at low doses of MOR, but those of DA in the striatum and NE in the spinal cord were decreased at high dose of MOR. These results suggest that the mechanism of eptazocine-induced analgesia is different from those of PZC and MOR in terms of the relationship to catecholamine neurons.

Analgesics↗
PubMed1981

[Pharmacological action of eptazocine (l-1,4-dimethyl-10-hydroxy-2,3,4,5,6,7-hexahydro-1,6-methano-1H-4-benzazonine). (III) Central action of eptazocine (author's transl)].

Pharmacological actions of eptazocine on the central nervous system were investigated by pharmacological and behavioral methods. Eptazocine produced sedation at low doses and Straub tail reaction in mice and ataxia in rats at high doses. In mice, eptazocine caused decreases in the spontaneous locomotor activities measured by the wheel cage and Animex methods, but caused an increase of the response in rats as determined by the open-field method. Eptazocine caused impairment of performance in the rotarod test and the traction test in mice, a decrease of activity of EMG, and an inhibition of flexor reflex in rats. Eptazocine decreased body temperature, potentiated pentobarbital-induced sleeping, and convulsion caused by pentylene-tetrazol in mice. Fighting behavior induced by electric shock and central stimulation effect of methamphetamine were inhibited by eptazocine in mice. Eptazocine showed an inhibiton of avoidance behavior in shuttle and skinner boxes in rats. These results suggest that eptazocine produces a non-specific inhibitory action on the central nervous system.

Analgesics↗
PubMed1981

Effect of chlorphentermine on the pulmonary disposition of norepinephrine in the isolated perfused rabbit lung.

Chlorphentermine (CP) has been noted to cause primary pulmonary hypertension both clinically and experimentally. It was postulated that CP might affect the pulmonary clearance of endogenous vasoactive substances such as norepinephrine (NE). The uptake and metabolism of 14C-NE were followed in artificially ventilated isolated perfused rabbit lung preparations using a constituted perfusate with initial NE concentration of 5 micrograms/100 ml. Perfusate samples were analyzed for total radioactivity, metabolites, and parent compound. Preloading the lungs with 0.25 mM CP significantly increased the concentrations of total radioactivity, deaminated products, and decreased the concentration of normetanephrine in the perfusate. In addition, the accumulation of total radioactivity in the lung tissue after 60 min of perfusion was significantly decreased in CP-treated lungs. The proportion of deaminated metabolites in the lung tissue was slightly decreased while the percent of normetanephrine, and parent compound were significantly increased by the CP treatment. CP (0.1 mM) also inhibited the in vitro metabolism of NE by 79%. These results provide experimental evidence in support of a hindered pulmonary clearance of circulating NE by CP.

Animals↗
PubMed1981

[Pharmacological action of eptazocine (l-1,4-dimethyl-10-hydroxy-2,3,4,5,6,7-hexahydro-1,6-methano-1H-4-banzazonine). (II) Relationship between the analgesic action of eptazocine and brain 5-hydroxytryptamine (5-HT) (author's transl)].

The relationship between the analgesic action of eptazocine and brain 5-HT was investigated by pharmacological and neurochemical methods in comparison with pentazocine (PZC) and morphine (MOR). The analgesic effects of eptazocine, PZC, and MOR as determined by the pressure method were decreased by pretreatment with rho-chlorophenylalanine or 5,6-dihydroxytryptamine. The analgesic effects of all three drugs were also diminished by a lesion in the dorsal half of the spinal cord (C5-6) or the raphe magnus. A lesion in the central gray produced a decrease in the analgesic effects of MOR or PZC, but had a weak effect on that of eptazocine. All three drugs increased 5-hydroxyindole acetic acid (5-HIAA) levels in the brain stem, the striatum, and the spinal cord. In addition, eptazocine decreased the 5-HIAA level in the cortex and the 5-HT level in the hippocampus, but increased the 5-HT level in the spinal cord. An increase of 5-HIAA in the cortex and a decrease of 5-HT in the brain stem were observed after PZC-administration. On the other hand, MOR decreased the 5-HT level in the brain stem and striatum. These results suggest that the effects of eptazocine on 5-HT neurons are similar to those of PZC and MOR, but part of the action mechanism of eptazocine is different from those of PZC and MOR.

Analgesics↗
PubMed1981

Neurochemical studies of an analgesic, 1,3-diphenyl-5-(2-dimethylaminopropionamide)-pyrazole [difenamizole].

For the purpose of clarifying the action mechanism of the analgesic agent, difenamizole (DFZ), chemically known as 1,3-diphenyl-5-(2-dimethylaminopropionamide)-pyrazole, the following properties were investigated: 1) monoamine metabolizing enzymes, 2) biosynthesis of dopamine (DA), 3) binding of DA on the synaptic membrane of mice, 4) uptake of catecholamine (CA) by synaptosome in discrete brain areas and 5) DA release from the striatal slices of mice. Pertinent results obtained are delineated below: 1) DFZ at 10(-4) M inhibited the monoamine oxidase (MAO) activity to some extent although it had no activity on catechol-O-methyltransferase (COMT) at 10(-6) -10(-4) M. 2) DFZ significantly enhanced the DA accumulating activity of pargyline in the striatum. 3) DFZ inhibited the binding of 3H-DA to synaptic membrane by 25% at 10(-4) M in the striatum. 4) DFZ inhibited the DA uptake by 50% at 10(-4) M though the activity was somewhat weaker than imipramine or cocaine on the striatum. 5) DFZ inhibited the DA release due to high K+ concentration in striatal slices at 10(-4) -5x10(-4) M. From the above data, it was concluded that DFZ may exert its analgesic effect by inhibiting the release of DA and preventing the binding of DA with the receptors.

Adenosine Triphosphatases↗
PubMed1981

Pharmacological responses to pentobarbital in different strains of mice.

This study was designed to assess the strain differences in pentobarbital toxicity, narcosis, the development of tolerance and physical dependence, the half-life of pentobarbital and the activities of hepatic microsomal electron transfer chain in DBA/2J, C57BL/6J and ICR mice. The comparisons of responses to acute pentobarbital-induced narcosis with two different doses revealed that DBA was most sensitive among these strains. When continuous administration of pentobarbital by pentobarbital pellet implantation is concerned, four criteria were used to assess strain differences: 1) determination of the duration of the loss of righting reflex during pentobarbital pellet implantation; 2) cumulative mortality after pentobarbital pellet implantation; 3) degree of tolerance development after 3 days of s.c. implantation of a 75-mg pentobarbital pellet by the relative decrease in the pentobarbital sleeping time; and 4) assessment of hyperexcitability by pentylenetetrazol- and audiogenic-induced seizures after pellet removal. The order of susceptibility to continuous pentobarbital pellet implantation was found to be as follows: DBA/2J > C57BL/6J > ICR. The biochemical data also revealed that the half-life of pentobarbital in DBA/2J mice was significantly longer than that of C57BL/6J or ICR mice in both brain and serum. Further studies also showed that DBA/2J mice have lower hepatic cytochrome P-450 and cytochrome b5 levels and NADPH dehydrogenase and NADPH-cytochrome c reductase activities as compared with the other strains of mice. However, these parameters were markedly induced in DBA/2J mice after the development of tolerance to pentobarbital. It appears that the differences in genetic variation could be of importance for further studies in gaining insight of the mechanism of barbiturate tolerance and dependence.

Animals↗
PubMed1981

[Application of a shuttle avoidance schedule in rats to evaluate a drug-induced auditory impairment (author's transl)].

In attempts to study drug-induced auditory impairment we measured the auditory threshold in rats, using the shuttle box method. The auditory threshold with physical impairment of ears was also measured. The sensitivity of the rats to the auditory response was decreased to about 15dB in cotton-stuffed ears and to about 20dB in pierced eardrums. In this experiment, we used drugs known to be ototoxic; dihydrostreptomycin sulfate, kanamycin sulfate, neomycin sulfate and ethacrynic acid. With successive administration of each drug, the auditory sensitivity in rats decreased. This shuttle box method is easily facilitated and the auditory threshold of many rats can be measured over a short period. This approach may be a useful method for screening ototoxic drugs.

Aminoglycosides↗
PubMed1980

Effects of 5-hydroxytryptamine on defecation in open-field behavior in rats.

An attempt was made to elucidate the role of the serotonergic nervous sytem in defecation resulting from environmental stimulation in rats. The open-field (OF) test and shuttle box method were used to study the defecation. 5-Hydroxytryptophan (5-HTP) significantly decreased the number of fecal boluses excreted in both emotional situations, namely, in both OF and shuttle box. The fecal excretion was significantly reduced compared with the controls after intraventricular injection of 5-hydroxytryptamine (5-HT). Animals pretreated with p-chlorophenylalanine (pCPA) and 5,6-dihydroxytryptamine (5,6-DHT) tended to show a slight increase in the OF defecation. 5-HTP was equally effective in diminishing the OF performance of pCPA-treated rats. The inhibitory effects of 5-HTP on the defecation were also observed after depletion of biogenic amines by reserpine treatment. Home cage defecation was increased after 5-HTP administration, decreased under pretreatment with pCPA and not influenced by intraventricular injection of 5-HTP. These results suggested that the defecation after environmental stimuli was due to a change in 5-HT levels in the brain.

5,6-Dihydroxytryptamine↗
PubMed1979

[Possible mechanism of morphine-induced Straub tail reaction (STR) (author's transl)].

Mechanical contraction of the dorsal sarco-cocygeus muscle and electrical stimulation of spinal cord elicited tail elevation such as straub tail reaction (STR). When morphine, 0.25 approximately 0.5 microgram, was injected into the lumbothecal space, STR was produced dose-dependently and such was the same as that produced by systemic injection of morphine. STR was not observed, when morphine was injected into the lumbo-thecal space in spinal mice. STR was antagonized by tubocurarine given subcutaneously and by naloxone injected into the lumbothecal space. STR was not antagonized by the right, left or both dorsal spinal lesion at C5 approximately 6 as well as by the right or both dorsal spinal lesion at T11 approximately 12. However, STR was antagonized by the spinal transection at T11 approximately 12. The lesion of spinal serotonergic neurons enhanced STR. These results suggest that morphine acts on both the lumbo-sacral nerve cell bodies and the nerve terminals descending via the spinal ventral horn, by which the morphine-induced contraction of dorsal sarco-coccygeus muscle tendons produce STR.

Analgesics↗
PubMed1978

[Application of a response duration schedule in rats to evaluate drug-induced auditory impairment (author's transl)].

Determination of auditory threshold was carried out under a response duration schedule of tone and/or light-dipper presentation. This schedule enabled an exact assessment of auditory sensitivity, since the direction and distance from rat to sound source were constant and the rat could thus acquire the conditioned behavior in a short time. The rat has to press the lever and hold it until a CS(tone and/or light) was presented. The animal could get water-reinforcement with release of the lever during the period of CS. The intensity of 3 KHz pure tone was reduced, from 110 dB (starting point), by 2 dB steps in each trial, until the subject made 3 non-response trials (i.e., no dipper approach within 0.7 sec after the tone onset) among 5 trials. The highest tone intensity among non-response trials was taken as the threshold. The auditory sensitivity of the rats with cotton-stuffed ears and the pierced eardrums decreased about 10 and 20 dB, respectively. The auditory sensitivity in rats was decreased by administration of streptomycin sulfate(SM), 300 mg/kg/day, i.m., in combination with ethacrynic acid(EA), 50 mg/kg/day, p.o., for forty days and in combination with EA, 100 mg/kg/day, p.o. for ten days. The auditory sensitivity was not influenced by administration of SM, 300 mg/kg/day, i.m., for forty days.

Acoustic Stimulation↗