Serotonin (5-HT) release in the dorsal raphé and ventral hippocampus: Raphé control of somatodendritic and terminal 5-HT release

Summary Somatodendritic and terminal release of serotonin (5-HT) was investigated by simultaneously measuring extracellular concentrations of 5-HT, 5-hydroxyindole-3-acetic acid (5-HIAA) and homovanillic acid (HVA) in the dorsal raphé and ventral hippocampus in freely moving rats. Perfusion of tetrodotoxin (TTX, 1M and 10M) into the dorsal raphé simultaneously decreased dorsal raphé and hippocampal 5-HT release. However, following TTX perfusion into the hippocampus (10M), hippocampal 5-HT release was profoundly reduced but dorsal raphé 5-HT remained unchanged.Systemic injections with the 5-HT_1a agonist, buspirone (1.0–5.0mg/kg, i.p.) decreased 5-HT and 5-HIAA and increased HVA concentrations in the dorsal raphé and in the hippocampus. The decreases in raphé and hippocampal 5-HT induced by systemic buspirone were antagonized in rats pretreated with 1.OmM (–) pindolol, locally perfused into the dorsal raphé. Local dorsal raphé perfusion of (–) pindolol alone (0.01–1.0mM) increased dorsal raphé 5-HT and concomitantly induced a small increase in hippocampal 5-HT. Buspirone perfusion into the dorsal raphé did not change (10 nM, 100nM), or produced a small increase (1.0mM) in raphé 5-HT, without changing hippocampal 5-HT.These data provide evidence that 5-HT release in the dorsal raphé is dependent on the opening of fast activated sodium channels and that dorsal raphé 5-HT_1a receptors control somatodendritic and hippocampal 5-HT release.     

Iontophoretic transdermal delivery of buspirone hydrochloride in hairless mouse skin

The transdermal delivery of buspirone hydrochloride across hairless mouse skin and the combined effect of iontophoresis and terpene enhancers were evaluated in vitro using Franz diffusion cells. Iontophoretic delivery was optimized by evaluating the effect of drug concentration, current density, and pH of the vehicle solution. Increasing the current density from 0.05 to 0.1 mA/cm² resulted in doubling of the iontophoretic flux of buspirone hydrochloride, while increasing drug concentration from 1% to 2% had no effect on flux. Using phosphate buffer to adjust the pH of the drug solution decreased the buspirone hydrochloride iontophoretic flux relative to water solutions. Incorporating buspirone hydrochloride into ethanol:water (50:50 vol/vol) based gel formulations using carboxymethylcellulose and hydroxypropylmethylcellulose had no effect on iontophoretic delivery. Incorporation of three terpene enhancers (menthol, cineole, and terpineol) into the gel and when combined with iontophoresis it was possible to deliver 10 mg/cm²/day of buspirone hydrochloride.     

丙戊酸镁缓释片与丁螺环酮治疗广泛性焦虑对照研究

目的探讨丙戊酸镁缓释片治疗广泛性焦虑障碍的疗效及安全性。方法将100例广泛性焦虑障碍患者随机分为两组各50例,研究组给予丙戊酸镁缓释片治疗,对照组给予丁螺环酮治疗,观察8w。于治疗前及治疗1w、2w、4w、8w末采用汉密顿焦虑量表、临床总体印象量表评定临床疗效,副反应量表评定不良反应。结果治疗8w末研究组总有效率为93.6%,对照组为91.7%,经Ridit分析两组总体疗效相当（z=1.059,P=0.273）。汉密顿焦虑量表评分研究组治疗1w末、2w末较对照组下降显著（t=-3.16,-3.08,P〈0.01）,临床总体印象量表评分研究组治疗1w末较对照组下降显著（t=-3.42,P〈0.01）。两组不良反应均轻微。结论丙戊酸镁缓释片治疗广泛性焦虑障碍起效快,疗效显著,安全性高,依从性好。     

新型载体聚己内酯对盐酸丁螺环酮缓释片释放的影响

 目的考察新型缓释载体材料聚己内酯对盐酸丁螺环酮缓释片中药物释放的影响。方法利用聚己内酯等为辅料,经湿法制粒制备盐酸丁螺环酮缓释片,并考察了不同相对分子质量和用量的聚己内酯对药物释放的影响。结果聚己内酯显示出良好的阻滞药物释放的性能,制备的缓释片能满足释放持续24h的设计用药要求。结论聚己内酯作为新型载体材料,适合于缓释片的阻滞剂。     

高效液相色谱法测定血浆中盐酸丁螺环酮及其活性代谢物的含量

目的:高效液相色谱法测定血浆中盐酸丁螺环酮及其活性代谢物1—嘧啶哌嗪浓度。方法:用 Hypersil BDS CN 色谱柱(4.6mm×150mm,5μm),以甲醇—四氢呋喃—磷酸盐缓冲液(15:15:70)为流动相,流速为1.5mL·mim~(-1),室温,紫外检测波长238nm,内标物为1—嘧啶哌嗪。结果盐酸丁螺环酮在10～200μg·mL~(-1)范围内,1—嘧啶哌嗪在10～200μg·mL~(-1)峰面积比与浓度线性关系良好,相关系数分别为0.9998和0.9994,回收率为97.58%～105.4%,RSD 均小于9%。本法灵敏度高,专属性好。     

九味虑平颗粒治疗广泛性焦虑症的临床疗效观察

目的:观察九味虑平颗粒治疗广泛性焦虑症(心脾两虚证)的临床疗效和安全性.方法:采用随机双盲双模拟阳性对照试验设计,将72例广泛性焦虑症(心脾两虚证)患者按3:1的比例随机分入九味虑平组(54例)和丁螺环酮组(18例)治疗4周,比较两组的临床疗效和不良反应发生率.结果:两组疗效相似,九味虑平组总有效率为94.34%,显效率为64.15%;丁螺环酮组总有效率100%,显效率77.78%.两组不良反应相似,不良反应发生率均为11.11%.九味虑平的主要不良反应有口干、便秘,个别病例出现心电图T波改变,但患者无自觉症状.结论:九味虑平颗粒用于治疗广泛性焦虑症(心脾两虚证)安全有效.     

丁螺环酮与帕罗西汀联合治疗抑郁症的效果

目的 探讨丁螺环酮与帕罗西汀联合治疗抑郁症的效果。方法 将符合ICD-10或CCMD-3抑郁症诊断标准的病人80例,随机分成两组,分别用丁螺环酮联合帕罗西汀（联合组）和单用帕罗西汀（单用组）治疗6周,采用汉密尔顿抑郁量表（HAMD）、汉密尔顿焦虑量表（HAMA）分别于治疗第1、2、4、6周末评定疗效,用副反应量表（TESS）评定不良反应。结果 第6周末联合组HAMD和HAMA评分低于单用组,第2周末、第6周末联合组的HAMD和HAMA平均减分率高于单用组,差异均有显著性（t=1．79～11．57,P〈0．05）。两组间的不良反应发生率差异无显著性。结论 丁螺环酮联合帕罗西汀治疗抑郁症的效果优于单用帕罗西汀。     

Dopamine D3 receptors as a therapeutic target for methamphetamine dependence

Background: Methamphetamine (MA) use disorders are major public health problems nationally and worldwide and treatment remains an unmet need. Objectives: (1) To review preclinical and clinical studies identifying the dopamine D3 receptor as a therapeutic target for substance use disorders (SUDs), including MA dependence, (2) to consider buspirone (Buspar®) as a potential medication based on its dopamine D3 receptor antagonist properties, and (3) to evaluate the safety and initial efficacy of buspirone in a pilot study of MA-dependent individuals. Methods: Literature on the dopamine D3 receptor as a therapeutic target and on the potential of buspirone as a novel therapy for MA dependence was reviewed. The cardiovascular and subjective effects of intravenous MA challenge were assessed in five non-treatment seeking individuals. Participants met DSM-IV criteria for MA dependence and were treated subacutely (9 days) with buspirone (60?mg daily). Results: The literature identified the dopamine D3 receptor as a therapeutic target for MA dependence, a safe and approved medication, and a valuable opportunity to re-purpose buspirone for treating MA dependence and perhaps other SUDs. Pilot data (n?=?5) indicated that buspirone is safe in MA-using individuals and comparison against historical placebo data from this laboratory suggested that at least some aspects of the subjective properties of MA may be diminished during buspirone treatment. Conclusion: Future studies should include a small-scale, placebo-controlled Phase IIa trial of buspirone in MA dependence.     

Hospital Management of Acute Iron Ingestion

Abstract

This overview summarizes the major and minor side effects and drug interactions of fluoxetine. The adverse reactions include the “serotonin syndrome”, cardiovascular complications, extrapyramidal side effects such as akathisia, dyskinesias, and parkinsonian-like syndromes and an apparently increased risk of suicidality. Fluoxetine-induced mania and hypomania, seizures and sexual disorders are evaluated along with minor symptoms of allergic reactions, stuttering, hematological changes, psoriasis, and inappropriate secretion of the antidiuretic hormone. The major fluoxetine-drug interactions involve the amino acids L-dopa and L-tryptophan, anorexiants, anticonvulsants, antidepressants, anxiolytics, calcium channel blockers, cyproheptadine, lithium salts, and drugs of abuse. The underlying mechanism and the paradoxical effects of fluoxetine are addressed.