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61.
62.
Per Hartvig S.Å. Eckernäs Leif Lindström Bengt Ekblom Ulf Bondesson Hans Lundqvist Christer Halldin Kjell Någren Bengt Långström 《Psychopharmacology》1986,89(2):248-252
By means of positron emission tomography the uptake and kinetics of N-(methyl-11C)clozapine in different brain regions have been studied in Rhesus monkeys. 11C-clozapine rapidly entered the brain and maximum radioactive uptake was seen 5–12 min after administration. Highest uptake was measured in the striatum. Other regions with an uptake higher than in the cerebellum were thalamus and mesencephalon. The radioactivity from different brain regions decreased with an elimination half-life of about 5 h and parallelled the plasma kinetics of unlabelled clozapine. The striatum/cerebellum ratio of 11C-clozapine-derived radioactivity remained constant during the period studied and did not change after pretreatment with atropine. In contrast, the striatum/cerebellum ratio was somewhat lower after pretreatment with N-methylspiperone (NMSP), indicating competition for the same binding sites in the striatum. After pretreatment with increasing doses of clozapine, a dose-dependent protection of binding sites in the striatum for 11C-NMSP was seen. It is concluded that clozapine is more loosely bound to dopamine receptors in the striatum than N-methylspiperone and that the kinetics of clozapine in the brain parallel that in the plasma. The binding properties of clozapine within the brain may explain some of the clinical properties of the drug. 相似文献
63.
本文从下丘脑、大脑皮层、海马等脑区去甲肾上腺素(NA)的含量,其合成酶与降解酶的活性、NA受体数目等多环节的测定来分析肾上腺素能神经递质系统在老化脑中的变化。实验结果表明衰老过程下丘脑、大脑皮层内NA合成酶活性没变化,NA含量明显增高,下丘脑内α_1受体数目显著减少。上述结果提示这些脑区肾上腺素能神经的活动有可能减弱。同时,海马内单胺氧化酶B(MAO B)活性明显增加,说明海马神经元外组织有增生的可能。泰文并讨论了这些变化与老年记忆、行为与神经内分泌等脑功能衰退的关系。 相似文献
64.
G. D'Agostino M. C. Chiari E. Grana 《Naunyn-Schmiedeberg's archives of pharmacology》1989,340(1):76-81
Summary The inhibitory effects of some muscarinic agonists on tritiated acetylcholine release evoked by field stimulation were investigated in the rat urinary bladder strip. The acetylcholine stores of the preparation were labelled with 3H-choline. Electrical field stimulation caused an outflow of tritium, reflecting the release of 3H-acetylcholine. The release of 3H-acetylcholine was decreased in a concentration-dependent manner by all the agonists tested: oxotremorine, muscarone, muscarine, carbachol and methylfurtrethonium. On the contrary, only muscarine and muscarone enhanced the basal efflux of tritium in a concentration-dependent fashion. Concentration-response curves were determined both at 2 Hz and at 1 Hz by using intermittent administration of the drugs. Maximal depression in release (by 78 – 82%) was observed in experiments at 1 Hz. A similar inhibition was obtained at 2 Hz frequency only when a low concentration of calcium (0.6 mM) in the medium was used. Oxotremorine was the most potent among the tested compounds with the same intrinsic activity as the other drugs. In contrast to the other agonists investigated, oxotremorine showed in about 10-fold greater potency at pre- than at postjunctional muscarine receptors in the rat urinary bladder. This difference might depend either on heterogeneity of muscarine receptors or on different mechanism(s) relating to the transducing properties of receptors at the pre- and postjunctional level. A comparison between the relative prejunctional potencies in the rat urinary bladder and in the guinea pig myenteric plexus (data from the literature) suggests that prejunctional muscarine receptors are similar in these tissues. Furthermore, the findings obtained with a low concentration of calcium in the medium may support the view that intraneuronal availability of calcium plays a significant role in modulating the prejunctional negative feed-back mechanism in the rat urinary bladder.Send offprint requests to Dr. G. D'Agostino at the above address 相似文献
65.
B. BEGAUD L. DANG TRAN J.L. MONTASTRUC and P. MONTASTRUC 《Fundamental & clinical pharmacology》1987,1(3):153-159
The cardiovascular effects of mesulergine were studied in anesthetized dogs. Intravenous (IV) administration (0.3 mg/kg) significantly decreased blood pressure in neurogenic hypertensive dogs without any change in heart rate. This effect was completely antagonized by IV administration of domperidone (0.5 mg/kg). Intracisternal administration of mesulergine (0.03, 0.3 and 3 mg/kg) did not produce any change in blood pressure. However, with the highest dose we observed a significant rise in heart rate during the first 2 min (which was probably nonspecific). These results suggest that mesulergine lowers blood pressure in sinoaortic-denervated dogs by means of a peripheral mechanism probably involving DA2 receptors. The findings confirm the potential interest of dopamine-receptor agonists as future antihypertensive agents. 相似文献
66.
The effect of lithium on slow wave sleep (SWS) was studied in ten normal male volunteers using home based cassette sleep recording and automatic sleep stage analysis. Lithium increased SWS, an effect consisten with a reduction in brain 5-HT2 receptor function. 相似文献
67.
W. Kropf K. Kuschinsky J. Krieglstein 《Naunyn-Schmiedeberg's archives of pharmacology》1989,340(6):718-725
Summary EEG activity after activation of dopamine receptors of D-1 and/or D-2 type was studied by using telemetric recordings in rats. Apomorphine, a preferential D-2 agonist, produced a characteristic increase in the power of alpha-1 band (7.00–9.50 Hz) when given in doses mediating stereotypies (0.2 or 0.5 mg/kg s. c.). Low doses produced a general increase in the power of all of the bands except beta-2. In particular, delta activity was enhanced which seems to be in correspondence with the sedation observed after these doses (0.02 and 0.05 mg/kg). Haloperidol in a dose which is assumed to block both D-1 and D-2 receptors (0.1 mg/kg i. p.) completely antagonized the alpha-1 activation produced by apomorphine (0.5 mg/kg). A similar, although not complete inhibition of alpha-I activation was found after administration of a large dose of the selective D-1 antagonist SCH 23390 (0.2 mg/kg i. p.). The selective agonist at D-2 receptors quinpirole (1.0 mg/kg s. c.) produced a less pronounced activation of the power in the alpha-1 band than apomorphine.In general, there was found to be a good correlation between the activation of the alpha-1 activity and stereotyped behaviour. The results suggest that for the full expression of alpha-1 activation, a pronounced activation of D-2 receptors and at least a minimal activation of D-1 receptors, for instance by the endogenous dopamine, is necessary.
Send offprint requests to K. Kuschinsky at the above address 相似文献
68.
For centuries snake venoms have been known to interfere with haemostasis and this is now known basically due either to toxins activating/inhibiting clotting factors, having effects on blood vessels or interfering with platelet function. In this short review, the interaction of one major group of toxins, the snake venom metalloproteinases, with platelets is considered. This is relevant for understanding the mechanism of haemorrhage induced by these toxins. 相似文献
69.
A Hatziefthimiou A Mitsacos E Mitsaki A Plaitakis E D Kouvelas 《Journal of neuroscience research》1991,28(3):367-375
In the present work the distribution of L-glutamate binding sites in the different layers of human cerebellum of normal individuals and of seven patients who died with olivopontocerebellar atrophy (OPCA) was examined with the technique of quantitative autoradiography. Specific L-[3H]glutamate binding was higher in the molecular than in the granule cell layer of normal cerebellar tissue. A significant decrease of L-[3H]glutamate specific binding was observed in the molecular layer of all OPCA tissues. In the granule cell layer L-[3H]glutamate binding was decreased only in two patients who suffered from late-onset sporadic OPCA and in one patient who suffered from a form of OPCA inherited in a dominant manner. Quisqualate-sensitive binding sites were the most abundant binding sites in the molecular layer of normal cerebella, whereas N-methyl-D-aspartic acid (NMDA)-sensitive binding sites were the most abundant type in the granule cell layer. A significant decrease of quisqualate-sensitive and an increase in NMDA-sensitive binding sites were observed in the molecular layer of OPCA cerebellar tissues. No significant changes were observed in the granule cell layer of these tissues. 相似文献
70.
Simona Cabib Claudio Castellano Vincenzo Cestari Umberto Filibeck Stefano Puglisi-Allegra 《Psychopharmacology》1991,105(3):335-339
Pretreament with small, per se ineffective doses of the selective D1 antagonist SCH 23390 inhibited hyperactivity induced by cocaine. On the other hand, the classic neuroleptic haloperidol and the selective D2 antagonist metoclopramide prevented the stimulatory effects of cocaine on locomotion only at hypokinetic doses, while the atypical neuroleptic (–)-sulpiride, a selective D2 antagonist, did not produce significant effects when administered at the hypokinetic dose of 12 mg/kg. Finally, at low doses (–)-sulpiride dose-dependently potentiated the locomotor-stimulating effects of cocaine, an effect that is not shared either with haloperidol or with metoclopramide. These results are discussed in terms of different roles of DA receptor subtypes in the modulation of the stimulant effects of cocaine on locomotion. 相似文献