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101.
SEVERO SALVADORI REMO GUERRINI PIERO ANDREA BOREA ROBERTO TOMATIS 《Chemical biology & drug design》1992,40(5):437-444
The synthesis of pseudotetrapeptides H-Tyr-D-Ala-Phe-NH-(CH2)2-NH2 (1a), H-Tyr-D-Ala-Phe-ψ(CH2-NH)-Gly-NH2 (2a), H-Tyr-D-Ala-ψ(CH2-NH)-Phe-Gly-NH2 (3a), and H-Tyr-ψ(CH2-NH)-D-Ala-Phe-Gly-NH2 (4a), representing the N-terminal tetrapeptide sequence of dermorphin, in which amide bonds are replaced by CH2-NH bond, is described. N-acetyl-Tyr and desamino-Tyr pseudopeptide analogs (1-4b), (1-3c) are also described. The analogs were assayed in binding studies based on displacement of μ and δ-receptor selective radiolabels from rat brain membrane and in a bioassay using guinea pig ileum (GPI). Pseudopeptides in which the C-terminal (1a) or D-Ala-Phe (3a) amide bond are substituted, exhibit higher μ-affinities and μ-receptor selectivity than the corresponding Phe-Gly or Tyr-D-Ala analogs (2a, 4a). Acetyl-and desamino-Tyr pseudopeptide analogs (1-4b) and (1-3c) did not exhibit μ and δ-opioid receptor affinity at nM concentration. The relevance of the single peptide replacement and of its association to acetylation or amino group elimination of Tyr, is discussed on the basis of a receptor model for μ and δ opioids. 相似文献
102.
Y Wahbi R Caujolle C Tournaire M Payard M.D. Linas J.P. Seguela 《European journal of medicinal chemistry》1995,30(12)
Aromatic ethers related to antifungal azole miconazole were synthesized and tested against various strains of Candida. We found that activity is related to the nature of the aromatic ring and the position of substituents on this ring. Activity is more strongly dependent on the substituent in the 2 position of the ethyl chain than on the aromatic group linked through the oxygen. Triazoles were always less potent than the corresponding imidazole analogues. 相似文献
103.
This study was performed to evaluate the effects of dynorphin A(1–13) antiserum when microinjected into an active hyperalgesic region within the rat brain stem. When administered within the dorsal posterior mesencephalic tegmentum (DPMT) of intact conscious rats, dynorphin A(1–13) antiserum produced rapid onset and persistent prolongation of a low intensity thermally evoked tail avoidance response (LITETAR). These analgesic actions of the dynorphin A(1–13) antiserum appeared to be dose dependent. These studies support previous hypotheses about the existence of tonically active brain stem opioid hyperalgesic processes. Further, the results provide indirect evidence for a potential role of brain stem dynorphin(s) in facilitating pain. 相似文献
104.
Summary A series of in vivo experiments were undertaken, relating functional (motor activity, body temperature), dopamine (DA) receptor binding and neurochemical (catecholamine synthesis and utilization, DA release) aspects of the pharmacology of SCH 23390 in the rat.The compound inhibited the locomotor hyperactivity, but not the hypothermia, induced by the potent DA stimulant DP-5,6-ADTN. Interstingly, SCH 23390 simultaneously failed to displace DP-5,6-ADTN from its binding sites in the rat striatum—used as a direct in vivo biochemical index of DA (D-2) receptor interaction. The spontaneous locomotion in non-pretreated rats was likewise inhibited by SCH 23390. The locomotor-suppressive action, but not the DP-5,6-ADTN-displacing capcity of the D-2 blocker haloperidol was significantly enhanced by SCH 23390, suggesting that motility can be suppressed by either enhanced D-1 or D-2 (postsynaptic) receptor blockade, but also that the D-1 and D-2 sites involved may be physically distinct.SCH 23390 only slightly altered in vivo neurochemical of DA synthesis, release and nerve-impulse flow, indicating that, while similar in suppressing dopaminergic behaviour, the D-1 antagonist is less effective than traditional neuroleptics as an activator of DA neuronal feedback mechanisms. The weak increases of DA synthesis and release nonetheless obtained were equal in magnitude (30–40%) in the limbic vs. striatal brain areas; also in this respect, SCH 23390 thus differs from classical neuroleptics, which generally display more marked effects in the striatum than in limbic tissue.No major changes in the in vivo indices of NA synthesis and utilization (or in 5-HT synthesis) were found after SCH 23390 administration, by and large supporting the DA receptor specificity of the compound.In summary, the studies demonstrated that SCH 23390 can offset and accentuate, respectively, behavioural consequences of D-2 receptor stimulation and blockade. Importantly, at the same time no direct interaction at the level of D-2 DA receptor sites in the striatum was detected. Only slight, D-2 antagonist-like, changes in neurochemical indices of dopaminergic activity were observed after D-1 receptor blockade by means of SCH 23390. With regard to DA agonist hypothermia, SCH 23390 was without effect per se, but (at a high dose) attenuated the action of the D-2 antagonist haloperidol. The observations may indicate that the complex interactions between central D-1 and D-2 receptor-controlled mechanisms that influence behaviour, neurochemistry, and possibly autonomic nervous expression, are not identical. 相似文献
105.
哒嗪酮酸类化合物的合成及其抗惊活性的研究 总被引:1,自引:0,他引:1
以a-酮戊二酸与水合肼与水合肼为原始原料合成了15个N-(3’-磷酸二乙酯丙基)-1,6-二氢-6-氧-3-哒嗪酰胺类化合物,并对它们进行了最大电休克发作(MES)实验,结果表明其中4个化合物表现出中等强度的抗惊活性。 相似文献
106.
M. Schmutz K. Klebs V. Baltzer 《Journal of neural transmission (Vienna, Austria : 1996)》1988,72(3):245-257
Summary The influence of antiepileptics on the evolution of rat amygdaloid kindling was studied.Under placebo conditions clonic convulsions and a spike-wave EEG pattern developed. Diazepam, clonazepam, clobazam and phenobarbital were most effective in suppressing the evolution of kindling; the effects of valproate sodium, ethosuximide and acetazolamide were somewhat less pronounced in this respect. Carbamazepine, oxcarbazepine and phenytoin, on the other hand, enhanced kindling development, i.e. the increase in duration of after-discharge was faster than in the placebo group. The results indicate that under the above experimental conditions drugs with no anti-absence component can be distinguished from those with an anti-absence component. The mechanism of action underlying the observed effects is not yet known; the hypothesis that under special conditions protective inhibitory neuronal activity can develop to absence type seizures is proposed. 相似文献
107.
A. M. Ibrahim 《Phytotherapy research : PTR》1992,6(3):155-157
The anthelmintic activity of aqueous extracts (0.25–50 mg/mL) from 14 plant species that represent seven families of the Sudanese flora was examined using the free living rhabditid nematode, Caenorhabditis elegans as a test organism. Extracts of Balanites aegyptiaca and Sesbania sesban were the most effective (LC50, 0.8 and 8.0 mg/mL, respectively). Extracts of Albizzia anthelmintica, Cymbopogen narvatus, Abrus precatorius, Rhyncosia minima, Striga hermonthica and Anogeissus leiocarpa (LC50, 9.5–84.6 mg/mL were less effective in this model test system. Extracts of six plant species, Albizzia malacophylla, Gardenia lutea, Physostigma mesoponticum, Salvadora persica, Xeromphis nilotica and Waltheria indica had no effect upon C. elegans survival. 相似文献
108.
用心肌细胞跨膜电位记录,证实高浓度Ba~■(4mol/L)可诱发豚鼠心室肌自发电活性,这种自发电活性主要来自延迟后除极电位(DAD)及触发活动,且可被维拉帕米(异搏定)阻断,提示DAD的产生与钙离子内流有关。 相似文献
109.
亚硝酸盐法测定超氧化物歧化酶活性 总被引:1,自引:0,他引:1
用亚硝酸盐、氰化钾抑制区别法测定样品中的 Cu,Zn-SOD 和 Mn-SOD,灵敏度高,重现性好,操作简便。实验表明,抑制率达50%时所需 SOD 的浓度为0.07 μg/ml,其批内和批间的变异系数分别为6.0%和5.5%,鸡肝 Cu,Zn-SOD 与 KCN 的抑制复合物的表观解离常数 K′为288.6±45.5 μmol。 相似文献
110.
In the past few years there have been numerous publications which have stressed the value of the dexamethasone suppression test (DST) as a diagnostic marker of endogenous depression. Our own studies in 333 psychiatric inpatients and 121 healthy subjects did not reveal a differential diagnostic use for the DST. This result is in good agreement with other results in the literature. Our data demonstrate that intervening variables such as severity of illness, weight loss, sleep disturbances, situational stress, drug and alcohol withdrawal, and the pharmacokinetics of dexamethasone have an important influence on DST results, regardless of the diagnostic classification. 相似文献