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91.
以环己酮为起始原料,经与苯肼缩合、氧化、Mannich 反应制得1,2,3,9-四氢-3-二甲胺基甲基-4H-咔唑-4-酮盐酸盐(5),后者再与2-甲基咪唑缩合、甲基化合成翁丹西隆,总收率为10.4%。  相似文献   
92.
The content of serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and norepinephrine (NE) was analysed in 71 human spinal cords obtained post-mortem. The highest content of 5-HT, 5-HIAA and NE was found in the lumbar enlargement of the spinal cord. 5-HT and 5-HIAA content increased from fetal to adult spinal cord whereas the content of NE decreased. Characteristic segmental distribution of measured monoamines was present in adult spinal cord only. In two patients spinal cord lesion led to the reduction in spinal cord content of 5-HT, 5-HIAA and NE and loss of characteristic segmental distribution of these substances. These results are in general agreement with observations on spinal cord of different animal species.  相似文献   
93.
In rabbit platelet rich plasma (PRP), 5-hydroxytraptamine (5-HT,0.03~3μmol/L) induced decrease in light transmission (DLT) dose-de pendently with centralization, as revealed by electron microscopy. However, 5-HT did not induced platelet aggregation and release reaction. 5-HT-induced DLT was inhibited by methysergide (0.3~30μmol/L), indomethacin (0.3~10μmol/L) and PGE_1 (0.01~0.3μmol/L) in a dose-dependent manner, but not EGTA(0.3~3mmol/L). Collagen(Coll), arachidonic acid (AA), adenosine diphosphate (ADP) and a stable thromboxane A2 analoge(STA_2) also induced DLT before aggregation by themselves, which was also inhibited by PGE_1, but not inhibited by EGTA except for Coll However,Coll-, AA-, STA_2-and ADP-induced DLT were reduced by pretreatment of PRP with 5-HT dose-depen-dently. The duration of DLT by Coll and AA were decreased from 151.4±5.93 sec and 15(?)38±0.60sec to 45.44±4.04 sec and 9.00±1.25 sec respectively ((?)±s(?) P<0.01), but not by ADP and STA_2, 3μmol/L of ADP-and 0.3μmol/L of STA_2-induced aggregation which was not accompanied with release reaction were enhanced by 5-HT pretreatment, but in those (Coil 5μg/ml, AA 100~200μmol/L and STA_2 1~3 μmol/L) with release reaction, the amount of adenosine triphosphate(ATP)were suppressed significantly (P<0.001) by 5-HT pretreatment without the effect on the magnitude of aggregation, The mobilization of cytosolic free calcium concentration ([Ca~(2+)]i) was observed after 5-HT treatment in single washed platelet, the results indicated that the basic level of [Ca~(2+)] i was 64.78±3.24nmol/L and this level was increased dose-dependently and significantly at 30 sec after administration of 5-HT and the time of peak value of [Ca~(2+)] i was at 90~100 sec.The similar time courses of suppression of ATP released during aggregation, in cases of Coll(5μg/ml), AA (200μmol/L) and STA_2(3μmol/L), by 5-HT were also found in the present experiment.  相似文献   
94.
With the method of rapid gel sequencing, the complete nueleotide sequence of Fasciolopsis buski 5S rRNA has been determined: AAC GGG AUG AAG CUA GAC AUG UGG CGG CCU AGU UGG AGG UCG GAA CUC GGA AGU UAA GGA AUG UUG GGC CUG GUU AGU ACU GGU AUG GGU GAC CUU GGG AAU ACC GGG UGU UGC GUC CA_(OH) This have been compared with 553 species of other organisms 5S rRNA sequences previously published and fitted to a secondary structural model.  相似文献   
95.
This study examined the effect of acute and chronic administration of the selective 5-HT3 receptor antagonist BRL 46470A, an analog of granisetron, on the number of spontaneously active dopamine (DA) cells in the substantia nigra pars compacta (A9 or SNC) and the ventral tegmental area (A10 or VTA) in the rat. In the A10 area, the acute administration of BRL 46470A decreased the number of spontaneously active DA cells at a dose of 0.1 mg/kg (0.28 μmol/kg) ip, yet increased the number of spontaneously active DA cells at a dose of 0.3 mg/kg (0.84 μmol/kg). The chronic administration (21 days) of BRL 46470A appeared to produce a multiphasic dose-response curve. Thus, the chronic treatment with BRL 46470A increased the number of spontaneously active A10 DA cells at 0.03 (0.084 μmol) and 0.3 mg/kg, but decreased the number of spontaneously active A10 DA cells at a dose of 0.1 mg/kg. In contrast, BRL 46470A did not decrease the number of spontaneously active A9 DA cells after either acute or chronic administration (0.01-0.3 mg/kg). However, BRL 46470A did increase the number of spontaneously active A9 DA cells at acute and chronic doses similar to those that were effective in A10. The iv administration of (+)-apomorphine (APO) not only failed to reverse the decrease produced by chronic administration of BRL 46470A at 0.1 mg/kg, but further decreased the number of spontaneously active A10 DA cells. Similar to the results obtained with granisetron, the pretreatment of naive rats with either 0.01 or 0.1 mg/kg iv of BRL 46470A significantly potentiated (2-fold) the suppressant action of APO on the basal firing rate of A10, but not A9 DA cells. Overall, our results indicate that similar to granisetron, chronic BRL 46470A at 0.1 mg/kg selectively decreases the number of spontaneously active A10 DA cells, via a mechanism not related to depolarization inactivation. Presently, it is not clear what factors may contribute to the multiphasic dose-response curve of BRL 46470A. © 1994 Wiley-Liss, Inc.  相似文献   
96.
Medifoxamine, an antidepressant agent which has an original chemical structure, has been shown through in vitro studies, utilising radioligand binding in tissue homogenates, to bind with moderately high affinity to 5-HT1c and 5-HT2 receptor subtypes and to 5-HT uptake sites (IC50 950, 980, and 1,500 nM, respectively). It has been shown to bind in vivo to rat brain 5-HT2 receptors after acute treatment with high dose (50 mg/kg, i.e., 133.9 μmol/kg). After 14 days continuous treatment with low dose (20 mg/kg, 53.6 μmol/kg), a decrease in the capacity of [3H]-5-HT uptake and a dose-dependent down-regulation of 5-HT2 receptors in rat cerebral cortex were observed. These results indicate that medifoxamine, which has been shown previously to act through dopaminergic systems, interacts also with central serotonergic neurotransmission and particularly with the 5-HT2 receptors, which could contribute to its antidepressant effect.  相似文献   
97.
An investigation has been made into the effect of 3,4-methylenedioxymethamphetamine (MDMA or ‘Ecstasy’) administration on the concentration of 5-hydroxytryptamine (5-HT), uptake of [3H]5-HT and [3H]paroxetine binding in rat cerebral cortex tissue. Four days after 2 injections of MDMA (20 mg/kg i.p., 6 hr apart) the concentrations of 5-HT and its metabolite 5-HIAA were reduced by 60%. The binding of [3H]paroxetine to the presynaptic 5-HT transporter was decreased and high affinity uptake of [3H]5-HT was reduced by a similar amount, indicating neurodegeneration of 5-HT terminals. Pretreatment with chlormethiazole (100 mg/kg i.p.), 10 min before each MDMA injection prevented the decrease in both [3H]parotextine binding and uptake of [3H]5-HT. The loss in 5-HT and 5-HIAA content was also attenuated. Pretreatment with dizocilpine (1 mg/kg i.p.) or haloperidol (2 mg/kg i.p.) also prevented the MDMA-induced loss of [3H]paroxetine binding and attenuated the loss of 5-HT and 5-HIAA content. All three compounds also decreased the degree of hyperthermia that follows MDMA administration, although previous studies suggest that the long term neurodegeneration is not associated with the acute hyperthermic response. These data support the findings of others that MDMA injection produces degeneration of 5-HT nerve terminals in the cortex, confirm that chlormethiazole, dizocilpine and haloperidol attenuate MDMA-induced neurotoxic loss of 5-HT and demonstrate for the first time that these compounds prevent the neurodegeneration of 5-HT nerve terminals that follows MDMA administration.  相似文献   
98.
99.
The pharmacokinetics and haemodynamic effects of isosorbide dinitrate (ISDN) have been investigated following administration of single doses as a sublingual (SL) spray (2.5 mg), sublingual tablet (5 mg) and peroral tablet (10 mg) in a randomised, placebo-controlled double-blind cross-over trial in 16 healthy volunteers.After the sublingual spray Cmax was higher (39.0 ng·ml-1) and tmax was shorter (3.9 min) than after the sublingual (22.8 ng·ml-1 and 13.8 min) and peroral (16.9 ng·ml-1 and 25.6 min) tablets. The AUC of ISDN did not differ following any of the three formulations (1031; 879; 997 ng·ml-1·min, for the spray, SL tablet and PO-tablet, respectively). Mononitrate metabolites of ISDN (IS-2-MN and IS-5-MN) and total nitrates in plasma increased in proportion to the administered dose. This indicates that the fraction of the dose absorbed was the same for all the formulations but that the extent of first-pass metabolism increased in the order sublingual spray < sublingual tablet < peroral tablet. Thus, compared to the spray, the relative bioavailability of ISDN was 48% and 28% from the sublingual and peroral tablets, respectively.The haemodynamic effects were quantified using the a/b ratio of the finger pulse wave and the systolic blood pressure and heart rate under orthostatic conditions. For the a/b ratio of the finger pulse, the maximal effect was higher (emax=130%) and the time to emax (temax) shorter (16.6 min) after the spray than the sublingual tablet (84.4% and 25.5 min) or peroral tablet (90.2 and 31.3 min). The onset of effect was within 3, 5 and 7.5 min after the spray, sublingual and peroral tablets, respectively. A larger change in the orthostatically-induced decrease in systolic blood pressure and increase in heart rate was obtained following peroral than sublingual administration despite the similar plasma concentrations of ISDN. This probably reflects the larger amount of pharmacodynamically active mononitrate metabolites formed after oral dosing. The integrated effect following administration of 2.5 mg ISDN as spray was similar to that of a sublingual tablet of 5 mg.  相似文献   
100.
Activity at 5-HT1 and 5-HT2 receptor sites influences sexual behavior in male and female rats. 5-HT3 antagonists reportedly have no effect on copulatory activity in rats of either sex although they influence a variety of other behaviors. The effects of 5-HT3 agonists on sexual behavior are unknown. The following experiments were undertaken to assess the influence of the 5-HT3 agonists 1-phenylbiguanide (PBG) and 2-methyl-serotonin (2-Me-5-HT) on sexual behavior, when administered intracerebroventricularly. Consistent with earlier reports indicating that 5-HT1 and 5-HT2 receptor activity influences reproductive activity in a sex-dependent manner, PBG was found to facilitate male, but not female, rat sexual behavior. 2-Me-5-HT, however, failed to modify either female or male rat sexual activity. Evidence that PBG, but not 2-Me-5-HT, induces carrier-mediated dopamine release suggests that the effect of PBG in male rats is due to dopaminergic mediation. Overall, the present data indicate that 5-HT3 receptor activation has only slight effects on rat sexual behavior.  相似文献   
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