赛赓啶对 KBV200细胞多药抗性的逆转作用

研究赛赓啶对KB_V200细胞多药抗性的逆转作用及逆转机制。在KB_V200细胞,采用MTT法,测出赛赓啶对长春新碱、阿霉素和鬼臼乙叉甙耐药的逆转系数分别为5.5,2.0和1.9,而对5-氟尿嘧啶、美法仑的细胞毒性作用无明显影响,表明赛赓啶为多药抗性逆转剂。荧光分光光度法测定表明,赛赓啶可使KB_V200细胞内阿霉素蓄积量增加。流式细胞荧光测定显示赛赓啶可增加罗丹明123的蓄积并减慢其外排。免疫细胞化学及狭缝杂交表明赛赓啶不影响KB_V200细胞的P-糖蛋白染色深度和 mdr1 RNA 表达水平。以上结果提示赛赓啶的多药抗性逆转机制是抑制P-糖蛋白泵的功能。     

赛庚啶对内毒素血症小鼠氧化损伤的对抗作用

目的:研究赛庚啶对内毒素(LPS)血症小鼠氧化损伤的对抗作用。方法:小鼠尾静脉注射LPS,造成内毒素血症模型,观察赛庚啶能否提高小鼠24h存活率,并测定血浆NO的水平,心、肝、肾和脑组织中SOD和GSH-Px活力以及脂质过氧化产物MDA含量。结果:赛庚啶预防给药能够显著提高致死量LPS攻击后小鼠24h的存活率,使血浆NO2-/NO3-的水平显著降低,其中高剂量组SOD和GSH-Px活力增高,MDA含量降低。低剂量组SOD活力增高,但肝和脑组织中MDA含量下降不明显,肝和肾组织GSH-Px活力无明显增高。结论:赛庚啶预防给药能够防治LPS血症,改善小鼠LPS血症时重要脏器氧化性损伤状态,抑制血浆NO水平过度升高。     

赛庚啶对大鼠胰岛B细胞内分泌功能的影响

目的　探讨赛庚啶对大鼠胰岛Ｂ细胞内分泌功能的影响。方法　应用放射免疫分析、生化分析法和电子显微镜研究赛庚啶（Ｃｙｐｒｏｈｅｐｔａｄｉｎｅ,Ｃｙｐ）对大鼠胰岛Ｂ 细胞内分泌功能的影响。结果　Ｃｙｐ ２．３ｍ ｇ／（ｋｇ·ｄ）,灌胃给药,连续用药 １０ｄ 可引起大鼠血清胰岛素含量降低（Ｐ＜ ０．０１）,而血糖水平则无显著改变。Ｃｙｐ ４．６ｍ ｇ／（ｋｇ·ｄ）,不但引起血清胰岛素含量显著降低,而且使血糖水平显著升高（Ｐ＜ ０．０１）。电镜观察,大鼠胰岛Ｂ 细胞超微结构亦呈退行性改变。结论　Ｃｙｐ 连续用药可抑制大鼠胰岛Ｂ 细胞的内分泌功能。     

Treatment of neuroleptic induced tardive dyskinesia with cyproheptadine

Zusammenfassung Cyproheptadin ist seit Jahren als Antimetabolit des Serotonins verwendet worden. Es wurde über eine Wirksamkeit desselben bei extrapyramidalen Hyperkinesien (von den Angelsachsen als tardive dyskinesia bezeichnet) nach Neuroleptika-Medikation berichtet. Wir behandelten 11 Patienten, die wegen chronischer Schizophrenie behandelt wurden und schwere Dyskinesien aufwiesen, Cyproheptadin (Periactinol®, Periactin) verabreicht. In vier Fällen verschwand unter dieser Medikation das extrapyramidale hyperkinetische Syndrom vollständig, bei vier weiteren Fällen trat eine befriedigende Besserung auf. Im Verlaufe der Therapie wurden keine nennenswerten Nebenwirkungen beobachtet, die eindeutig auf das Cyproheptadin zurückzuführen gewesen wären.     

Hallucinogen-induced rotational behavior in rats

LSD, mescaline, and MDMT (5-methoxy-N,N-dimethyltryptamine) in normal rats induced dose-dependent rotation (circling behavior), which was consistent in direction from week to week (1 week separating hallucinogen administration). The direction of LSD-induced rotation for individual animals was the same as amphetamine-induced, but not apomorphine-induced, rotation. Of the three postsynaptic serotonin antagonists (methysergide, cyproheptadine, and 2-bromo-LSD) tested, only methysergide induced rotation; this rotation was consistent in direction from week to week, and was in the same direction as LSD-induced rotation. l-LSD induced weak rotation and was approximately six times less potent than d-LSD. p-Chlorophenylalanine pretreatment increased the sensitivity to LSD, whereas -methyl-p-tyrosine pretreatment blocked LSD-induced rotation. Simultaneous administration of LSD and amphetamine induced rotation significantly greater than amphetamine alone; a similar effect was observed with LSD plus scopolamine. However, apomorphine plus LSD induced rotation similar in magnitude to apomorphine alone. These results suggest that the mechanism by which hallucinogens induce rotation is consistent with an inhibitory action on the serotonin-containing midbrain raphe neurons. The inhibition of raphe neuronal firing could disinhibit nigrostriatal activity (possibly at the level of the substantia nigra). Methysergide-induced rotation could result from partial antagonism of postsynaptic serotonin receptors in the substantia nigra or striatum. The dopaminergic properties of LSD may attenuate rotation resulting from disinhibition of nigrostriatal activity by interacting with presynaptic nigrostriatal dopamine autoreceptors.     

Anticonvulsant efficacy of antihistamine cyproheptadine in rats exposed to the chemical warfare nerve agent soman

Organophosphate compounds, such as soman and sarin, are highly toxic chemical warfare nerve agents that cause a build-up of acetylcholine in synapses and neuromuscular junctions. Current therapies aim to prevent seizures and protect against brain injury following exposure. The present study was designed to evaluate the effectiveness of the antihistamine cyproheptadine in improving survival and controlling seizures in rats exposed to soman. Rats were pretreated with the oxime reactivator HI-6 (125 mg/kg, ip) 30 min prior to soman exposure (225 μg/kg, sc) and then treated with atropine methylnitrate (AMN, 2.0 mg/kg, im) 1 min after soman. Cyproheptadine (10, 13, 16 or 20 mg/kg, ip) was given at one of three time points: 1 min after soman intoxication, at the onset of soman-induced seizures or 5 min after seizure onset. Control animals were exposed to soman and given an equivalent volume of sterile water instead of cyproheptadine. The incidence of seizures, mortality, neuron counts, neuropathology and apoptosis in specific regions of the brain were evaluated. In animals given HI-6 and AMN the incidence of soman-induced seizure and mortality rate within the first 24 h were 100%. When cyproheptadine was given at a dose of 13 or 20 mg/kg 1 min after soman exposure, the incidence of seizures was reduced from 100% to 13% and 30%, respectively. In addition, cyproheptadine given at 1 min after soman exposure increased the survival rate to 100% regardless of dose. When cyproheptadine was administered at seizure onset, seizures were terminated in 100% of the animals at doses above 10 mg/kg. The survival rate with cyproheptadine treatment at the onset of seizure was ≥83%. Seizures terminated in ≥75% of the animals that received cyproheptadine 5 min after soman-induced seizure onset. When given at 5 min after seizure onset the survival rate was 100% at all tested doses of cyproheptadine. The neuropathology scores and the number of TUNEL positive cells in the brain regions examined decreased at all time points and cyproheptadine doses tested. These observations indicate that cyproheptadine treatment can effectively control seizures, improve survival, reduce seizure duration and reduce the number of dying cells in the brain following soman exposure.     

Serotonin syndrome in patients with peripheral neuropathy: a diagnostic challenge

According to the Hunter Serotonin Toxicity Criteria, the presence of either clonus or hyperreflexia is a must for making a diagnosis of serotonin syndrome (SS). We report five patients with SS who had areflexia because of associated polyneuropathy. None of the patients fulfilled the Hunter criteria for SS. However, all five patients had features suggestive of neuromuscular hyperactivity, autonomic hyperactivity and altered mental status and fulfilled the Sternbach criteria for SS. All patients responded to cyproheptadine within 5 days to 2 weeks duration. These cases highlight the limitations of the Hunter criteria for SS in patients with associated polyneuropathy.     

The effect of cyproheptadine on hunger,calorie intake and body weight in man

The appetite stimulating action and the weight gaining potential of one month's treatment with the antihistamine and antiserotonergic compound cyproheptadine (Periactin) 4 mg three times daily was compared to placebo in a double-blind crossover trial in sixteen thin but otherwise normal volunteers who wanted to gain weight. Subjects gained significantly more weight on cyproheptadine than on placebo. There was also a corresponding relative increase in subjective hunger ratings and food intake during the period on active drug. Drowsiness was the most frequent side effect observed. These findings are discussed in relation to a possible serotonergic feeding mechanism.     

Differential regulation of rat peripheral 5-HT<Subscript>2A</Subscript> and 5-HT<Subscript>2B</Subscript> receptor systems: influence of drug treatment

Most studies of 5-HT₂ receptor regulation have been carried out on the central nervous system (CNS) (which expresses 5-HT_2A and 5-HT_2C receptors); very few in vitro studies have addressed the peripheral receptors 5-HT_2A and 5-HT_2B. The aim of this investigation was to compare the possible short- and long-term processes regulating these peripheral receptors in the rat.The in vitro contractile response elicited by serotonin (5-HT, 10 µM) in the rat gastric fundus (5-HT_2B receptor system) was rapid and followed by a partial fade to a steady state, in contrast with the rat thoracic aorta response (5-HT_2A receptor system), which was more stable, slower and sustained. To characterize drug-receptor interactions, cumulative concentration/response curves (CCRCs) for 5-HT were constructed ex vivo for rat tissues treated with drugs acting at these receptors. Rats were examined 4 or 24 h after a single, i.p. administration of (±)1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane [(±)DOI, 1 or 2.5 mg/kg], clozapine, cyproheptadine or rauwolscine (10 mg/kg), 48 h after a single i.p. administration of (±)DOI (2.5 mg/kg), clozapine or cyproheptadine (10 mg/kg) or 24 h after the last of with 15 daily i.p. administrations of (±)DOI (1 or 2.5 mg/kg), clozapine, cyproheptadine or rauwolscine (10 mg/kg). In the aorta, E_max (the maximum response elicited by 5-HT) was unchanged 4 h after a single dose of any of the drugs tested. However, 24 h after a single dose, E_max was lower in animals treated with (±)DOI (2.5 mg/kg), clozapine or cyproheptadine than in controls, whilst 48 h after a single dose of (±)DOI (2.5 mg/kg), clozapine or cyproheptadine there was no difference in E_max between experimental and control animals. After chronic treatment with (±)DOI (2.5 mg/kg), clozapine and cyproheptadine, E_max was lower than in controls. In the gastric fundus, E_max 4 h after a single dose of each drug was lower than in controls, and the response recovered by 24 or 48 h. Following chronic treatment, E_max was significantly lower than in controls for each drug used.These findings suggest first, that regulation of peripheral 5-HT₂ receptors (5-HT_2A and 5-HT_2B) is a functionally significant phenomenon in vivo, and occurs after administration of both agonists and antagonists. Second, the kinetics of peripheral 5-HT₂ receptor regulation were similar in both in vivo and ex vivo experiments. The 5-HT_2B receptors in rat gastric fundus are more sensitive to drug-induced regulation than the 5-HT_2A rat aortic receptors. Finally, long-term regulation of both receptors stabilizes short-term desensitization for longer.     

晕痛定、赛庚啶、复方丹参注射液三联疗法治疗小儿偏头痛69例疗效观察

目的探讨晕痛定、赛庚啶、复方丹参注射液三联疗法治疗小儿偏头痛的临床疗效。方法 69例患儿随机分为治疗组35例和对照组34例。对照组给予赛庚啶、谷维素口服;治疗组给予晕痛定、复方丹参注射液、赛庚啶联合治疗。2组疗程均为2周。观察2组疗效及不良反应。结果治疗组总有效率为97.14%高于对照组的82.35%,差异有统计学意义(P<0.05)。治疗组发生轻度恶心、嗜睡2例,对照组发生食欲及体质量增加、嗜睡、口干7例,2组均无其他不良反应发生。结论晕痛定、赛庚啶、复方丹参注射液三联疗法可有效改善偏头痛症状,减少发作频率并预防发作,是治疗小儿偏头痛的有效方法。