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71.
72.
Hugh J Herdon Jeffrey C Jerman Tania O Stean Derek N Middlemiss Wai N Chan Antonio K Vong John M Evans Mervyn Thompson Neil Upton 《British journal of pharmacology》1997,121(8):1687-1691
- SB-204269 (trans-(+)-6-acetyl-4S-(4-fluorobenzoylamino)-3,4-dihydro-2,2-dimethyl-2H-benzol[b]pyran-3R-ol, hemihydrate) shows potent anticonvulsant activity in a range of animal seizure models, with a lack of neurological or cardiovascular side-effects. The profile of the compound suggests that it may have a novel mechanism of action. This study describes the characteristics of a binding site for [3H]-SB-204269 in rat forebrain membranes.
- Specific [3H]-SB-204269 binding was saturable and analysis indicated binding to a homogenoeous population of non-interacting binding sites with a dissociation constant (KD) of 32±1 nM and a maximum binding capacity (Bmax) of 253±18 fmol mg−1 protein. Kinetic studies indicated monophasic association and dissociation. Binding was similar in HEPES or Tris-HCl buffers and was unaffected by Na+, K+, Ca2+ or Mg2+ ions. Specific binding was widely distributed in brain, but was minimal in a range of peripheral tissues.
- Specific [3H]-SB-204269 binding was highly stereoselective, with a 1000 fold difference between the affinities of SB-204269 and its enantiomer SB-204268 for the binding site. The affinities of analogues of SB-204269 for binding can be related to their activities in the mouse maximal electroshock seizure threshold (MEST) test of anticonvulsant action.
- None of the standard anticonvulsant drugs, phenobarbitone, phenytoin, sodium valproate, carbamazepine, diazepam and ethosuximide, or the newer anticonvulsants, lamotrigine, vigabatrin, gabapentin and levetiracetam, showed any affinity for the [3H]-SB-204269 binding site. A wide range of drugs active at amino acid receptors, Na+ or K+ channels or various other receptors did not demonstrate any affinity for the binding site.
- These studies indicate that SB-204269 possesses a specific CNS binding site which may mediate its anticonvulsant activity. This binding site does not appear to be directly related to the sites of action of other known anticonvulsant agents, but may have an important role in regulating neuronal excitability.
73.
The effects of acute and chronic stages of carrageenan-induced air-pouch inflammation on the pharmacokinetics of prednisolone were studied in male Wistar rats. Chronic inflammation produced a significant increase in the area under the curve (AUC) of prednisolone compared to control animals (6594 ± 2144 vs 3530 ± 2164 µg · hr/ L). The effect of acute inflammation was not significant (AUC = 4996 ± 3813). Both acute and chronic inflammation also reduced thein vitro plasma protein binding of prednisolone, the reduction being much greater after chronic inflammation. The AUC of free prednisolone after chronic inflammation was 3141 µg · hr/L, compared to 1121 µg · hr/L in the control group and 1823 µg · hr/L after acute inflammation. The mean values of half-life and apparent volume of distribution at steady-state in each group were similar. These results indicate that prednisolone must be used with caution in the treatment of inflammatory diseases because of higher free concentrations of the steroid. 相似文献
74.
Susan De Santi Ph.D. Mony J. de Leon Ed.D. Antonio Convit M.D. Chaim Tarshish M.S. Henry Rusinek Ph.D. Wai Hon Tsui M.S. Elia Sinaiko Ph.D. Gene-Jack Wang M.D. Elsa Bartlet Ph.D. Nora Volkow M.D. 《The Psychiatric quarterly》1995,66(4):357-370
While many neuropsychological studies have demonstrated age-related performance alterations in tests thought to reflect frontal and temporal lobe function, there is little direct observation and comparison of these hypothesized brain changesin vivo. The cerebral glucose metabolism of frontal, temporal, and cerebellar regions was examined in 40 young (
=27.5±4.9) and 31 elderly (
=67.6 ± 8.8) normal males using PET-FDG. Univariate analysis showed age-related metabolic reductions in all frontal and temporal lobe regions. The reductions ranged from 13%–24% with the greatest changes in the frontal lobes. Multiple regression analyses showed a stronger age relationship with frontal lobe than with temporal lobe metabolism. The dorsal lateral frontal lobe was the region that appears to change most within the frontal lobes. Examination of the temporal lobe showed that age contributed equally to the metabolic variance of both the lateral temporal lobe and hippocampus. These results suggest that age-related metabolic changes exist in both frontal and temporal lobes and that the frontal lobe change is greater. 相似文献
75.
The aim of the study was to evaluate the usefulness of the magnetic resonance (MR) perfusion maps in the detection of liver tumor perfusion following transcatheter arterial chemoembolization (TACE). MR dynamic susceptibility contrast-enhanced imaging was performed in 12 patients with 10 confirmed hepatocellular carcinoma and 2 confirmed hepatic metastasis using single-shot echoplanar pulse sequence. Time-intensity curves for all hepatic tumors showed a transient signal drop and the hepatic blood volume (HBV) maps were reconstructed. On the HBV maps, most tumors (80%) demonstrated hyperperfusion before TACE and hypoperfusion following TACE. The site and the degree of residual hyperperfusion within the tumor on the HBV maps correlated well with the areas of hypervascularity on the angiograms. In conclusion, the MR perfusion maps can be a promising technique for detecting the perfusion of the residual tumor tissue following TACE. 相似文献
76.
Hypertrophic olivary degeneration (HOD) is a rare type of neuronal degeneration involving the dento-rubo-olivary pathway. It is distinguished from other types of neuronal degeneration in that hypertrophy, rather than atrophy, takes place in the neurons in the inferior olivary nucleus. Prior to the invention of Magnetic Resonance Imaging (MRI), HOD was difficult to be detected, and a firm diagnosis could only be made at autopsy. We present a case of bilateral HOD following surgical excision of a cavernous hemangioma in the brainstem. The literature and imaging findings of this uncommon condition are reviewed. 相似文献
77.
The anti-emetic potential of CP-122,721 ((+)-2S,3S)-3-(2-methoxy-5-trifluoromethoxybenzyl)amino-2-phenylpi peridine), CP-99,994 ((+)-(2S,3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine), CP-100,263 ((-)-(2R,3R)-3-(2-methoxybenzylamino)-2-phenylpiperidine), RP 67580 ((3R, 7aR)-7,7-diphenyl-2-[1-imino-2-(2-methoxyphenyl)ethyl] po-hydroisoindol-4-one), FK 888 (N2-[(4R)-4-hydroxy-1-(1-methyl-1H-in-dole-3-yl)carbonyl-L-propyl] -N-methyl-N-phenylmethyl-1-3-(2-naphthyl)-alaninamide) and GR 82334 ([D-Pro9[spiro-g-lactam]Leu10]-physalaemin-(1-11)) was investigated to inhibit nicotine (5 mg/kg, s.c.)-, copper sulphate pentahydrate (120 mg/kg, intragastric)- and motion (4 cm horizontal displacement at 1 Hz for 5 min)-induced emesis in Suncus murinus. A 30 min intraperitoneal pre-treatment with CP-122,721, CP-99,994, RP 67580 and FK 888 significantly (P < 0.05) antagonized nicotine-induced emesis with ID50 values of 2.1, 2.3, 13.5 and 19.2 mg/kg, respectively CP-100,263, the less active enantiomer of CP-99,994, was inactive at doses up to 10 mg/kg. Infusion of GR 82334, CP-122,721, CP-99,994 and FK 888 into the dorsal vagal complex of the hindbrain also antagonized nicotine-induced emesis yielding ID50 values of 1.1, 3.0, 3.3 and 58.0 microg/dorsal vagal complex, respectively RP 67580 and CP-100,263 were inactive. RP 67580 and FK 888 failed to antagonize copper sulphate-induced emesis but CP-122,721 and CP-99,994 were active yielding ID50 values of 2.2 and 3.0 mg/kg, i.p., respectively. CP-99,994 also completely prevented motion-induced emesis at 10 mg/kg, i.p. (P < 0.05) and RP 67580 produced a significant reduction of motion-induced emesis at 10 mg/kg, i.p. (P < 0.05). These studies provide evidence of a central site of action of tachykinin NK1 receptor antagonists to inhibit nicotine-induced emesis in S. murinus and confirm the broad profile of inhibitory action. The rank order of potency of the antagonists following the intra-dorsal vagal complex administration suggests that the S. murinus tachykinin NK1 receptor has a unique pharmacological profile. 相似文献
78.
Acute catatonic syndromes occurring in the context of various medical and neuropsychiatric conditions, including schizophrenia,
have been shown to respond well to benzodiazepines (BZD). However, there have been no studies specifically designed to address
the BZD treatment response of persistent catatonic states. Eighteen patients with clinically stable chronic schizophrenia,
who also displayed enduring catatonic features, underwent a 12-week long, random assignment, double-blind, placebo-controlled
cross-over trial with lorazepam (6 mg/day). A comprehensive assessment, including the subjects’ clinical and motor (catatonic
as well as drug-induced movement disorders) condition, was performed at baseline and four weekly intervals thereafter. Pre-existing
medication was kept constant throughout the study. Lorazepam had no effect on the subjects’catatonic signs and symptoms, suggesting
that acute and chronic catatonic syndromes associated with schizophrenic illness might have a different neurobiological basis.
Received: 25 May 1998/Final version: 22 September 1998 相似文献
79.
A methanolic extract of the whole plant of Elephantopus mollis was found to contain lupeol, lupeol acetate, epifriedelinol, molephantin, and 2-de-ethoxy-2-methoxyphantomolin, as well as a new sesquiterpene lactone determined to be 2-de-ethoxy-2-hydroxyphantomolin. 相似文献
80.
Fujino S Tezuka N Sawai S Konishi T Inoue S Kato H Mori A Okabe H 《Breast cancer (Tokyo, Japan)》1996,3(3):205-208
A case of glycogen-rich clear cell carcinoma (GRCC) which arose in the right breast of a 35-year-old Japanese woman is reported. Light microscopic examination of the tumor revealed solid alveolar proliferation of clear cells containing abundant glycogen. Electron microscopy identified aggregates of glycogen particles and numerous empty glycogen lakes. This case is reported with a discussion on the other 42 GRCC cases reported in the international literature. 相似文献