间歇性偏头痛预防性治疗新药-Erenumab

Erenumab(商品名:Aimovig)是第1个获得FDA批准的新型偏头痛预防性治疗药物,主要通过阻断降钙素基因相关肽(Calcitonin gene-related peptide,CGRP)受体,抑制CGRP的活性而发挥作用。与传统治疗偏头痛急性期的药物相比,Erenumab可以有效预防慢性和间歇性偏头痛的发作,减少发作次数,且有良好的耐受性和较少的禁忌证。本文对Erenumab的作用机制、药动学、药效学、临床评价和安全性等方面进行综述,为临床治疗和深入研究提供参考。     

成人偏头痛预防性治疗药物——Eptinezumab-jjmr

Eptinezumab-jjmr是由灵北公司开发的一种单克隆抗体,可阻断降钙素基因相关肽(CGRP)与其内源性受体结合,从而预防偏头痛的发作.2020年2月21日,美国食品药品管理局(FDA)批准Eptinezumab-jjmr用于成人偏头痛的预防性治疗.本文对Eptinezumab-jjmr的药理作用与机制、药物代谢...     

偏头痛预防性治疗新药人源化单克隆抗体galcanezumab

偏头痛是神经系统常见疾病,全球有超过10%的人口患有偏头痛,至今未得到充分诊断和治疗。2018年9月27日FDA批准galcanezumab作为人源化单克隆抗体上市,用于成人偏头痛的预防性治疗。现对其作用机制、药动学、临床研究及安全性等做一综述。     

预防性治疗偏头痛新药——阿托吉泮(atogepant)

偏头痛是世界范围内最常见的神经血管疾病,偏头痛患者约占全球人口的14％.病情反复发作,每月4～72 h,通常为搏动和单侧,伴有恶心、呕吐和声/光敏感性,强度为中至重度.偏头痛发作时可能十分严重,使患者丧失行动能力,对生活有实质性的影响.2016年全球疾病负担研究组(GBD)将其列为全球第二大致残性疾病,作为"残疾生活年...     

偏头痛治疗新药ubrogepant的药理作用与临床评价

偏头痛是最常见的神经系统疾病之一,严重影响患者的生活质量.2019年12月FDA批准降钙素基因相关肽受体拮抗剂ubrogepant上市,用于成人偏头痛(有或无先兆)急性期治疗.临床研究显示,ubro-gepant在给药2 h后可迅速消除疼痛及其相关症状(恶心、呕吐、畏光及恐声),可持续缓解疼痛长达24 h,安全性和耐受...     

治疗偏头痛的降钙素基因相关肽受体拮抗药:zavegepant北大核心CSCD

Zavegepant是2023年3月由美国食品药品监督管理局批准的首个降钙素基因相关肽(CGRP)受体拮抗药鼻腔喷雾剂,用于成人有先兆或无先兆偏头痛的急性治疗。Zavegepant是一种高选择性的CGRP受体拮抗药,最常见的药物不良反应主要为味觉障碍、恶心、鼻腔不适和呕吐。本文对zavegepant的作用机制、药代动力学、临床研究及安全性等方面进行介绍。     

治疗偏头痛的降钙素基因相关肽受体拮抗剂rimegepant

Rimegepant是百时美施贵宝公司开发的口服小分子降钙素基因相关肽(Calcitonin gene receptor peptide,CGRP)受体拮抗剂.该药已于2020年3月被美国食品药品监督管理局(FDA)批准上市,被推荐用于治疗有或无先兆的偏头痛急性发作.与曲坦类药物不同,rimegepant没有血管收缩特...     

Rimegepant的药理作用及其治疗偏头痛的临床研究现状

Rimegepant是一种降钙素基因相关肽(CGRP)受体拮抗药,2020年2月美国食品药品管理局(FDA)批准Rimegepant用于偏头痛的治疗.得益于较长的半衰期、良好的口服生物利用度以及对人CGRP受体的高亲和力,Rimegepant成为潜在治疗抗急性偏头痛的一线药物.Rimegepant是目前批准上市的第2款...     

降钙素基因相关肽(CGRP)抗体治疗偏头痛

降钙素基因相关肽(Calcitonin gene-related peptide,CGRP)是参与偏头痛发病机制的一种重要的神经肽,具有扩血管的作用。针对CGRP的治疗在临床试验中获得了显著的效果,而且不引起血管收缩,对心血管疾病患者相对安全。最早合成的药物是小分子量CGRP受体拮抗剂,主要用于偏头痛急性期的治疗,但因肝脏毒性使其研发过程屡屡受挫,目前尚无该类药物获得上市批准。随后出现的CGRP单克隆抗体在预防治疗发作性偏头痛和慢性偏头痛的临床试验中显示出充分的疗效和安全性,目前已经有3个单克隆抗体获得上市批准。本文主要对CGRP与偏头痛的关系以及CGRP单克隆抗体治疗偏头痛进行综述。     

偏头痛新药靶向降钙素基因相关肽（CGRP）单抗药物的非临床评价要点

偏头痛是一种常见的神经系统疾病,以单侧搏动性头痛为主要特征。降钙素基因相关肽（CGRP）在偏头痛的发病机制中发挥重要作用,并由此开发了用于偏头痛的CGRP拮抗药物,近期有3个以CGRP单抗或CGRP受体的单抗药物Aimovig^®、Ajovy^®和Emgality^®被FDA批准上市。概述了这3个单抗新药的非临床研究内容,并结合ICH S6（R1）分析了生物制品类新药非临床研究的要点,以期为国内该类药物的研发提供参考。     

Fremanezumab for the preventive treatment of migraine in adults

ABSTRACT

Introduction: The Calcitonin Gene-Related Peptide (CGRP) has been implicated in migraine pathophysiology due to its role in neurogenic inflammation and transmission of trigeminovascular nociceptive signal. New molecules targeting CGRP and its receptor have been developed as migraine-specific preventative treatments. Fremanezumab (or TEV-48,125, LBR-101), a human monoclonal antibody against CGRP, has been recently approved for clinical use by FDA and EMA.

Areas covered: This paper briefly discusses the calcitonin family of neurotransmitters and resultant activation pathways and in-depth the chemical properties, pharmacodynamics, pharmacokinetics, clinical efficacy and safety of Fremanezumab for the prophylactic treatment of migraine.

Expert opinion: Fremanezumab, a migraine-specific drug, is effective and safe as a prophylactic treatment of chronic and episodic migraine. As a monoclonal antibody, it was not associated to liver toxicity and is not expected to interact with other drugs. The long half-life might improve patients’ compliance. Long-term effects of CGRP block in cardiovascular, grastrointestinal and bone functions should be evaluated in ongoing trials, since CGRP is involved in multiple biological activities in the human body. Nevertheless, targeting CGRP itself allows the receptor binding with other ligands involved in several physiological functions. Thus, the long-term treatment with Fremanezumab is expected to be associated with a lower risk of severe adverse effects.     

偏头痛的预防性药物联合治疗

偏头痛是一种慢性的神经血管疾病,具有反复及周期性发作的特点。本文列举了钙拮抗剂、β-受体阻滞剂、抗抑郁药、抗癫痫药、镁剂、辅酶类、维生素类以及中药类等多种药物之间联合应用以预防性治疗偏头痛。因其临床效果满意,医师不妨参考借鉴。     

Anti-allergic properties of pipethiaden--a new preventive agent for migraine

Pipethiadene, a prophylactic of vasomotoric headaches of the series of 4,9-dihydrothieno(2,3-c)-2-benzothiepine derivatives, shows a peripheralpharmacological profile of an antiallergic agent. The experiments in rats showed a high antianaphylactic effect of pipethiadene in the passive cutaneous anaphylaxis (PCA) test. Pipethiadene also exerted intensive antianaphylactoid action in rats on the liberator of histamine, compound 48/80, on dextran, and in the use of a combination of ovalbumin with indomethacin. In comparative pharmacological experiments with pizotifen and cyproheptadine an attempt was made to estimate the relative role of histamine and 5-hydroxytryptamine 5-HT) mediators in the employed experimental procedures in rats.     

Zolmitriptan: a new acute treatment for migraine

Zolmitriptan is a new oral acute treatment for migraine. It is a selective and potent agonist at the serotonin (5-HT)(1B/1D) receptor and was developed to improve on the oral bioavailability, tissue selectivity and CNS penetration of earlier compounds. Animal studies confirmed that these objectives had been attained. In man, zolmitriptan is rapidly absorbed after oral administration, with at least 75% of the eventual C(max) reached within 1 h. Oral bioavailability is approximately 40%. The elimination half-life of zolmitriptan is approximately 2.5 h and the primary route of elimination is metabolism, with one of the metabolites being pharmacologically active. A consistent 2-h headache response rate of 60-70% was observed at doses of 2.5 mg and above. Long-term treatment response is high (> 80%) and consistent. In addition, there is evidence from electrophysiology in migraineurs that zolmitriptan has a central action not shared by sumatriptan. Zolmitriptan is well-tolerated. The nature and incidence of the most frequently reported adverse events are similar to those of other 5-HT(1B/1D) agonists. Long-term zolmitriptan usage was associated with an improvement in quality of life. Zolmitriptan is a suitable first-line drug for acute treatment for migraine.     

galcanezumab预防性治疗偏头痛疗效与安全性的Meta分析

目的评价galcanezumab预防性治疗偏头痛的疗效和安全性。方法计算机检索OVID、 PubMed、Cochrane图书馆、中国知网、万方和维普等数据库;同时检索百度学术等网站,筛选galcanezumab预防性治疗偏头痛有效性和安全性的随机对照试验(RCT),采用Stata 12软件进行Meta分析。结果共纳入5项RCT, 2 801例患者。Meta分析结果显示, galcanezumab组每月偏头痛日数(MHDs)变化(WMD=-1.75, 95%CI:-2.06～-1.44, P=0.000, I2=24.2%),偏头痛失能评估总分变化(WMD=-7.96, 95%CI:-10.71～-5.21, P=0.000, I~2=0.0%), MHDs减少≥50%、 75%、 100%的例数等方面均优于安慰剂组(均P <0.05)。galcanezumab组尿路感染、恶心、鼻咽炎和注射部位疼痛等不良反应与安慰剂组比较均无显著差异(P> 0.05)。结论现有证据表明galcanezumab预防性治疗偏头痛安全、有效。     

fremanezumab预防性治疗偏头痛有效性和安全性的Meta分析

目的评价fremanezumab预防性治疗偏头痛的有效性和安全性。方法计算机检索PubMed、Embase、 Web of Science (SCI)、 Clinical Trials Website、 Cochrane Library、中国知网、万方、维普等数据库中关于fremanezumab预防性治疗偏头痛有效性和安全性的随机对照试验(RCT),采用Stata 14软件对数据进行Meta分析。结果共纳入4项RCT, 1 715例患者。Meta分析结果显示,与安慰剂组比较,fremanezumab组在每月偏头痛日数、每月头痛日数、每月急性头痛用药日数减少等方面均优于安慰剂组(P <0.05)。fremanezumab组的总不良事件、与治疗相关的不良反应的发生率均高于安慰剂组(P <0.05);与安慰剂组比较, fremanezumab组在严重不良反应、因不良反应终止试验、注射部位疼痛或红斑、上呼吸道感染、尿路感染等方面均无显著差异(P> 0.05)。结论现有证据表明fremanezumab能有效地减少每月偏头痛、头痛和急性头痛用药的时间,不良反应可耐受。     

治疗产后抑郁症的新药：别孕烯醇酮

别孕烯醇酮是由Sage公司开发的γ-氨基丁酸A型受体的别构调节剂,于2019年3月被美国食品和药物管理局批准上市,是全球第一个也是唯一一个专门用于治疗产后抑郁症的神经甾醇类药物,有关不良反应包括头痛、头晕和嗜睡。     

治疗肾性贫血新药罗沙司他

慢性肾脏病（CKD）会导致肾性贫血,严重的肾性贫血会增加患者的死亡率。2017年10月18日FibroGen公司宣布国家食品药品监督管理总局（CFDA）已受理其提交的口服新药罗沙司他（Roxadustat,FG-4592）的上市申请,如获批准,将成为全球第一个低氧诱导因子（HIF）脯氨酰羟化酶（PH）抑制剂类的首创新药,中国将成为最先批准的国家。罗沙司他是一种新型HIF-PH酶抑制剂,通过稳定HIF,抑制其降解,从而激活相关基因的转录,产生相应的生理反应,发挥抗肾性贫血的作用,而且疗效显著,不良反应少,给药方便,可减少或规避铁剂的使用。介绍罗沙司他的作用机制、药动学、临床研究、不良反应等研究进展,为临床应用提供参考。     

Inhaled drug therapy development for the treatment of migraine

Introduction: The inhalation of substances, both medicinally and recreationally, is a commonly used method of drug administration but has been underutilized in the treatment of neurologic disorders such as migraine. Three drugs have been studied as potential inhalable treatments for acute migraine: dihydroergotamine (MAP0004), prochlorperazine (Staccato prochlorperazine), and loxapine (Staccato loxapine).

Areas covered: This review discusses the available literature describing the pharmacokinetics, tolerability and efficacy of MAP0004, Staccato prochlorperazine and Staccato loxapine, including data from Phase II and Phase III clinical trials.

Expert opinion: Inhaled DHE offers rapid absorption with a pharmacokinetic profile similar to IV administration. Improved side effect profile results from more selective binding at antimigraine serotonergic receptors 5-HT_1B and 5-HT_1D. Inhaled prochlorperazine is rapidly absorbed and resulted in statistically significant migraine pain relief at 2 hours compared to placebo but is not currently being pursued by the manufacturer as a potential migraine abortive. Inhaled loxapine is also rapidly absorbed into systemic circulation but Phase IIb trials did not show statistically improved pain relief or pain freedom compared to placebo. MAP0004 will likely provide a good alternative to patients seeking rapid relief without the need for injection or other invasive routes.