新型抗精神病药阿立哌唑的临床评价

目的：探讨阿立哌唑的临床特点及其应用前景,为临床提供参考。方法：通过查阅、学习国内外有关文献,加深对阿立哌唑的临床作用及不良反应的了解;通过收集北京市近3年来非典型抗精神病药的应用数据,计算分析其应用趋势。结果与结论：阿立哌唑疗效确切,不良反应少,安全性高,应用人群逐年增多,临床应用前景广阔。     

抗精神病药物阿立哌唑临床应用评价

大量临床研究证实,阿立哌唑作为一种具有全新作用机制的非典型抗精神病药物,治疗精神分裂症疗效肯定,不易复发,不良反应小,是临床上较有价值的治疗药物.笔者就近几年国外对该药的临床研究和评价进行了综述.     

非典型抗精神病新药阿立哌唑的合成

目的：研究非典型抗精神病药阿立哌唑的合成路线及工艺。方法：通过优化反应溶剂、反应温度、反应时间及加料方式，以1-(2，3-二氯苯基)哌嗪盐酸盐为起始原料，经N-溴丁基化和O-烃基化合成了阿立哌唑。结果：合成了目标化合物，总收率85％，其化学结构经元素分析、红外光谱、核磁共振氢谱及质谱确证。结论：该方法适合工业化生产。     

抗精神病药阿立哌唑的合成工艺改进

目的改进抗精神病药阿立哌唑的合成工艺。方法以间氨基苯甲醚为原料,经酰胺化、傅-克烃化、醚化、N-烷基化四步反应合成阿立哌唑。结果通过优化条件合成了阿立哌唑,总收率40%,目标化合物的结构经元素分析、质谱、氢谱、红外光谱确证。结论改进后的工艺操作简便,易于控制,且节省了反应时间,降低了生产成本,更有利于工业化生产。     

新型抗精神病药阿立哌唑及其市场展望

1 精神分裂症 精神分裂症是一种脑疾,其特征为患者精神功能异常且伴行为混乱。精神分裂症的人口发病率约在1％左右,其中绝大多数患者年龄介于15～45岁间。精神分裂症的临床表现包括妄想、幻想和思想混乱等阳性症状与避离社交和缺乏动机等阴性症状,以及诸如工作记忆等基本认知     

阿立哌唑的合成

1-(2,3-二氯苯基)哌嗪盐酸盐与4-溴丁酸乙酯经N-烷基化、硼氢化钠还原制得1-[(4-羟基)丁基]-4-(2,3-二氯苯基)-哌嗪(5),5经对甲苯磺酰化得到的对甲苯磺酸4-[4-[(2,3-二氯苯基)哌嗪-1-基]丁酯(6)与7-羟基-3,4-二氢-2(1H)-喹啉酮缩合得到阿立哌唑,总收率约76%.     

阿立哌唑的合成

间氨基酚和3-氯丙酰氯制得的酰胺在无水三氯化铝作用下环合得7-羟基-3,4-二氢-2(1H)-喹诺酮,与1,4-二溴丁烷成醚后与1-(2,3-二氯苯基)哌嗪进行取代反应制得抗精神病药阿立哌唑,总收率25%.     

阿立哌唑的合成

目的合成抗精神病药阿立哌唑,并验证所用路线的中间体的螺环季铵盐结构。方法1-（2,3-二氯苯基）哌嗪盐酸盐与1,4-二溴丁烷反应后,再与7-羟基-3,4-2（1H）-喹喏啉酮反应。结果总收率达45%,目标化合物经核磁共振氢谱和红外确证结构,并验证了中间体结构,化学名为5,8-二氮杂螺[4,5]癸烷溴化物。结论此工艺路线生产成本低,反应条件温和、适宜工业化生产。并确证了中间体是5,8-二氮杂螺[4,5]癸烷溴化物,而非1-（4-溴丁基）-4-（2,3-二氯苯基）哌嗪。     

阿立哌唑的合成

7-羟基-3,4-二氢-2（1H）-喹诺酮和4-溴-1-丁醇经醚化制得7-（4-羟基丁氧基）-3,4-二氢-2（1H）-喹诺酮，再经磺酰化、1-（2，3-二氯苯基）哌嗪取代制得抗精神病药阿立哌唑，总收率77．5％。     

Pharmacological, pharmacokinetic and clinical properties of olopatadine hydrochloride' (olopatadine), an antiallergic drug

Olopatadine is a selective histamine H1-receptor antagonist possessing inhibitory effects on the release of inflammatory lipid mediators such as leukotriene and thromboxane from human polymorphonuclear leukocytes and eosinophils. Olopatadine also inhibited the tachykininergic contraction in the guinea pig bronchi by prejunctional inhibition of peripheral sensory nerves. Oral administration of olopatadine inhibited passive cutaneous anaphylaxis in rats, experimental allergic rhinitis and bronchial asthmatic responses in actively sensitized guinea pigs. Olopatadine exerted no significant effects on action potential duration in isolated guinea pig myocardium and ventricular myocytes. Olopatadine was highly and rapidly absorbed in healthy volunteers. The urinary excretion of olopatadine accounted for not less than 58% and the contribution of metabolism was low in the elimination of olopatadine. Olopatadine was shown to be useful for the treatment of allergic rhinitis and chronic urticaria in double-blind clinical trials. Olopatadine was approved in Japan for the treatment of allergic rhinitis, chronic urticaria, eczema dermatitis, prurigo, pruritus cutaneous, psoriasis vulgaris and erythema exsudativum multiforme in December, 2000.     

55例抗精神病药物的不良反应报告分析

目的了解抗精神病药物引起的不良反应,为深入开展药品不良反应监测工作提供依据。方法对该院2008年6月～2009年5月收集的55例抗精神病药物的不良反应报告进行回顾性分析。结果利培酮引起的不良反应最多见,有16例,占29．1％;神经系统损害最常见。结论临床应重视抗精神病药物引起的不良反应,须定期监测、及时上报,其可为临床治疗提供参考,以期减少或避免药品不良反应的发生。     

Pharmacological,toxicological and neurochemical effects of Δ2(E)-valproate in animals

TheE isomer of 2-ene-valproic acid (Δ^2(E)-VPA) is the major active metabolite of the antiepileptic drug valproate (VPA) in various species, including humans. Experimental studies on Δ^2(E)-VPA and VPA indicate that Δ^2(E)-VPA may be a useful antiepileptic drug itself. Δ^2(E)-VPA has the same wide spectrum of anticonvulsant activity as VPA with a somewhat higher anticonvulsant potency in rodent and dog models of different seizure types. As VPA, Δ^2(E)-VPA increases presynaptic γ-aminobutyric acid (GABA) levels in the brain, presumably by an effect on GABA synthesis and/or GABA degradation. Δ^2(E)-VPA is a much more potent inhibitor of the human brain GABA-degrading enzyme than VPA. In high doses. Δ^2(E)-VPA is more sedative in rodents than is VPA; LD50 values are about the same. In mouse and rat models for teratogenicity, Δ^2(E)-VPA does not induce teratogenic effects, whereas VPA is teratogenic in these models. Pilot rat studies on liver toxicity of VPA and VPA metabolites suggest that Δ^2(E)-VPA is not hepatotoxic. In view of the rare but serious hepatotoxicity and teratogenicity of VPA in humans, Δ^2(E)-VPA obviously merits interest as a valuable alternative drug in antiepileptic therapy.     

Pharmacological and toxicological studies on new Rh(I) organometallic complexes.

New rhodium(I) complexes, belonging to the general structure [Rh(CO)2 (L)], where dithiocarbamate and xanthate derivatives, were synthesized and assayed as cytostatic and antitumour agents in vitro against KB cells and in vivo against P388 leukaemia, Ehrlich ascites carcinoma, Sarcoma 180 ascites and ADJ/PC6A solid tumour. Assays against five trypanosoma strains were also performed. Among the new compounds the [Rh(CO)2 (DPA-dtc)] appeared to be active in all biological systems without showing evident nephrotoxicity.     

Pharmacological and toxicological properties of ryodipine

2,6-Dimethyl-3,5-dimethoxycarbonyl-4-(o-difluoromethoxy-p hen yl)-1,4-dihydropyridine (ryodipine, PP-1466) causes lasting decrease in systolic and diastolic arterial pressure at intravenous and oral administration to anesthetized animals. In conscious rats with DOCA-salt (des-oxycortone) and spontaneous hypertension, as well as in rats with hypertension provoked by method of cellophane perinephritis, PP-1466 (1 and 10 mg/kg, orally) decreases systolic pressure considerably. Therapeutic doses of PP-1466 do not essentially affect rhythm and frequency of cardiac contractions. High doses of the drug increase the heart rate. PP-1466 increases coronary blood flow. PP-1466 antagonizes considerably the pressor effect of angiotensin. In this respect PP-1466 is superior to SKF-24260 (2,6-dimethyl-3,5-diethoxycarbonyl-4-(o-difluoromethylphenyl)-1, 4-dihydropyridine). PP-1466 reduces hypotensive reaction and tachycardia induced by isoprenaline administration, inhibits decrease in arterial pressure caused by electric stimulation of the vagus nerve and administration of acetylcholine. Hypotension caused by PP-1466 and its negative inotropic effect can be antagonized with calcium chloride. In mice and rats PP-1466 at doses exceeding 10 mg/kg exerts a certain dose dependent depressant effect on the CNS. More protracted depressant effect on the CNS is exerted by nifedipine which was studied parallelly. In rabbits oral PP-1466 decreases in EEG basic rhythm amplitude both in cortical and subcortical structures. High doses of the drug lead to dysrhythmia in bioelectric activity. Acute, subacute and chronic toxicity studies in mice, rats and dogs show that PP-1466 possesses low acute toxicity and is well tolerated at protracted repeated administration of therapeutic and several times higher doses.     

Pharmacological properties of tiropramide, an antispasmodic drug

1. The pharmacological properties of an antispasmodic drug, tiropramide, were studied in isolated smooth muscle preparations. 2. Tiropramide at concentrations of 10(-6) to 10(-4) M relaxed various smooth muscles contracted spontaneously and by smooth muscle stimulants or electrical stimulation. Tiropramide did not interact with all drug-receptors examined, suggesting a pure musculotropic smooth muscle relaxant activity. 3. Tiropramide was found to inhibit both Ca uptake and Ca release in the guinea pig urinary bladder. 4. Tiropramide is considered to be useful to inhibit the contractile response of the urinary bladder, as this organ is mainly innervated by noncholinergic excitatory neurons.