A Pivotal Phase III trial of Phaxan™, a new formulation of alphaxalone dissolved in sulfobutyl ether beta cyclodextrin, for anaesthesia in patients undergoing hip joint replacement; stage 1, the pilot study

开始日期2018-04-12

申办/合作机构-

ACTRN12611000343909

/ Completed临床1期

Induction of anaesthesia with an intravenous injection of PHAX001, a new water soluble anaesthetic compared with propofol for speed of onset and recovery from anaesthesia.

开始日期2013-11-14

申办/合作机构

Southern Health Partners, Inc.

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100 项与阿法沙龙相关的临床结果

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100 项与阿法沙龙相关的转化医学

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100 项与阿法沙龙相关的专利（医药）

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项与阿法沙龙相关的文献（医药）

2026-08-01·AMERICAN JOURNAL OF VETERINARY RESEARCH

Intravenous lidocaine administered in the dorsal occipital sinus was ineffective for euthanasia of Asian box turtles (Cuora spp)

Article

作者: Tovar-Lopez, Gretel ; Kunzman, Hannah ; Hawkins, Shawna ; Kleinschmidt, Laura ; Stilwell, Jacob

Abstract:

Objective:

Determine the ability of IV lidocaine and pentobarbital to induce rapid euthanasia.

Methods:

In this blinded, randomized study, Asian box turtles ( Cuora spp) designated for euthanasia were sedated with alfaxalone before euthanasia with lidocaine (20 mg/kg) or pentobarbital (200 mg/kg) IV in the dorsal occipital sinus over a 3-day period. The sinus was located by ventral flexion of the head with needle insertion ventral to the supraoccipital crest. Time to loss of cardiorespiratory and neurologic function was documented. Supplemental doses were administered at 30-, 60-, and 90-minute time points if the heartbeat persisted. Pentobarbital was administered regardless of treatment group at the 90-minute time point.

Results:

15 Asian box turtles were assigned to lidocaine (8) and pentobarbital (7) treatment groups. Intravenous injections were successfully administered in the dorsal occipital sinus. Turtles given lidocaine had cessation of heartbeat at varying time points but had spontaneous return of heartbeat; all required pentobarbital 90 minutes after initial injection to induce permanent cardiac arrest. The majority of the pentobarbital group (5 of 7) had a permanent loss of heartbeat.

Conclusions:

The dorsal occipital sinus was reliable and easily accessible for high-volume injections. Lidocaine IV, even at high doses, was ineffective for euthanasia. In contrast, pentobarbital IV produced repeated rapid loss of detectable heartbeat.

Clinical Relevance:

This study highlights the successful administration of IV medications through a more easily accessed venipuncture site, the dorsal occipital sinus. Pentobarbital is reliable and efficient for euthanasia; however, higher doses than the current published guidelines are recommended for rapid cardiac arrest in reptiles.

2026-06-01·Journal of the American Association for Laboratory Animal Science

Alfaxalone-Based Anesthetic Combinations to Minimize Anesthesia-Induced Transient Lens Opacity in Rats (Rattus norvegicus)

Article

作者: Yamagiwa, Yoshinori ; Yamashita, Atsuko

Anesthesia-induced lens opacity has been reported in rats and mice and is characterized as acute and reversible. In ophthalmologic research, lens opacity often interferes with the accurate acquisition of ocular data. In this study, we investigated the usefulness of alfaxalone, an anesthetic known for its favorable safety profile, for prevention of anesthesia-induced lens opacity in rats. First, anesthetic protocols using alfaxalone were screened to identify those suitable for the study. Then, the induction profiles of transient lens opacity following intraperitoneal administration of alfaxalone–butorphanol and alfaxalone–midazolam–butorphanol were evaluated, and the findings were compared with those obtained for ketamine–xylazine, which is known to induce lens opacity. Lens opacity induced by alfaxalone-based anesthetic combinations was significantly milder than that induced by ketamine–xylazine. Alfaxalone-based anesthetic combinations suppressed reflex responses, and alfaxalone–midazolam–butorphanol provided sufficient depth and duration of anesthesia for morphology-based assessment of the eye, although the depth of anesthesia was lower than that achieved with ketamine–xylazine. In conclusion, the combination of alfaxalone, midazolam, and butorphanol may represent a promising anesthetic option for ophthalmologic studies in rats.

2026-06-01·VETERINARY JOURNAL

Choosing wisely: Effects of propofol and alfaxalone induction on maternal and neonatal outcomes in isoflurane-anesthetized dogs undergoing cesarean section

Article

作者: Antończyk, Agnieszka ; Ligocka-Kowalczyk, Zuzanna ; Ochota, Małgorzata

METHODS:

Thirty-five bitches undergoing elective CS were randomly assigned to propofol-isoflurane (PROP, n = 17) or alfaxalone-isoflurane (ALFA, n = 18) induction. Maternal vital signs and isoflurane requirements were monitored intraoperatively. Umbilical cord blood samples were analyzed for gases and electrolytes. Neonatal vitality was assessed using a modified Apgar score at 0, 5, and 20 min.

RESULTS:

Both protocols provided generally stable anesthesia, but hypotension episodes were more frequent in ALFA dams after fetal removal (44.4% vs. 17.7%) and at the closure (66.7% vs. 17.7%). Isoflurane requirements were higher in the ALFA group. Neonates from ALFA dams showed higher umbilical cord pH (7.19 ± 0.09 vs. 7.16 ± 0.08) and lower pCO₂ (64.4 ± 16.0 vs. 72.3 ± 16.6 mmHg). At 20 min, Apgar scores were significantly higher in the ALFA group (8.22 ± 0.95 vs. 7.79 ± 0.59). All puppies survived the first week of life.

CONCLUSIONS:

Alfaxalone induction was associated with reduced neonatal acidosis and improved vitality compared with propofol, though it increased maternal isoflurane requirements and hypotension risk later in surgery. Alfaxalone-isoflurane may offer neonatal advantages, but close monitoring of maternal blood pressure is essential.

项与阿法沙龙相关的新闻（医药）

2026-06-01

·暨南epilepsy center

抗癫痫药物发现史系列四||GABAA受体选择性正变构调节剂

西诺氨酯--GABAA受体选择性PAM 西诺氨酯双通道作用机制自西诺氨酯（Cenobamate）于2026年四月份在中国上市以来，基于西诺氨酯独特的双通道作用机制和国际多中心的III期临床试验数据，西诺氨酯突破了既往药物难治性癫痫疗效的天花板，给药物难治性癫痫患者带来了新希望（图1）。有关西诺氨酯作用于钠通道，抑制持续性钠电流的神经机制不难理解；而西诺氨酯是GABAA受体选择性正变构调节剂这一新作用机制令很多人费解。笔者为弄清这一机制，颇费周折，觅得诸多佳图并进行了加工修改，非常有助于我们理解其中重要的名词和概念。图1.西诺氨酯双通道作用机制要理解这一机制，还得从抗癫痫药物作用的传统靶点GABAA受体说起。众所周知，GABA是抑制性神经递质，与突触后膜GABAA受体结合后导致氯离子通道开放，大量氯离子内流产生抑制性突触后电位（IPSP），从而抑制突触前或突触后神经元的兴奋性。因此GABA能系统一直是抗癫痫药物研发的重要靶点（图2）。图2.GABA系统是抗癫痫药物重要的靶点近年来，抗癫痫药物研发更是聚焦于GABAA受体选择性正变构调节剂 (Positive Allosteric Modulator，PAM)方向，催生了一系列选择性更强、疗效更佳、副作用更小的新型抗癫痫药物、抗焦虑药、催眠药（图3），GABA能系统焕发出新生机。图3.GABAA受体选择性正变构调节剂 GABAA受体结合位点两分法一、按照所结合的配体分类 GABAA受体上有很多结合位点，按所结合的配体种类，可分为GABA、苯二氮卓类（Benzodiazepine）、巴比妥类（Barbiturates）、神经类固醇（Neurosteroids）、麻醉剂结合位点等（图4-5）。图4.GABAA受体上底物结合位点(截面图）图5.GABAA受体上底物结合位点(侧面图）二、按结合位点的功能可分为正构（Orthosteric）和变构（Allosteric）位点两类，这两类位点的相互作用决定了神经信号的抑制强度。 1. 正构位点（Orthosteric Site）：正构位点又称主动位点，是内源性配体结合并直接激活受体的区域（图6）。图6.正构抑制示意图 ①位置：通常位于受体五聚体结构a与β亚基之间的交界面（图4、5）； ②配体：内源性激动剂：神经递质 GABA；激动剂/拮抗剂：如蝇蕈醇（激动剂）、荷包牡丹碱（拮抗剂）。 ③效应：当GABA结合于正构位点时，受体构象改变，氯离子通道开放，氯离子内流使神经元超极化，产生抑制性突触后电位（IPSP），从而降低神经元的兴奋性。 2. 变构位点（Allosteric Site）：变构位点是不同于正构位点的其他受体区域，变构调节剂（Modulators）结合于此，不直接激活通道，但结合后通过改变受体三维构象，从而调节正构激动剂（GABA）亲和力或通道开放的频率/持续时间。 ①位置：位于正构位点以外的独立区域，种类繁多，不同变构调节剂对应不同的结合位点。 ②配体及类别：正变构调节剂 (Positive Allosteric Modulator，PAM)：又称变构激活、结合到GABAA受体变构位点，导致GABAA受体构象发生改变，利于GABA与GABAA受体的结合，氯离子通道开放、氯离子内流，产生抑制性突触后电位（EPSP）（图7）。图7.变构激活示意图负变构调节剂 (Negative Allosteric Modulator，NAM)：又称变构抑制、结合到GABAA受体变构位点，导致GABAA受体构象发生改变，阻碍GABA与GABAA受体的结合（图8）。图8.变构抑制示意图 β-咔啉类（如 DMCM），结合于苯二氮䓬位点，产生致焦虑或致惊厥作用。竞争性抑制剂：氟马西尼（Flumazenil）可特异性结合苯二氮䓬变构位点，竞争性阻断苯二氮䓬类或β-咔啉的作用，但本身无正或负调节效应。非竞争性抑制剂：如印防己毒素（Picrotoxin），直接结合在氯离子通道内孔，阻断氯离子通行。总结正构配体（GABA）决定了受体通道的基础开关，而变构调节剂则像“调光器”，通过结合变构位点来放大（正变构）或缩小（负变构）GABA 信号的强弱。临床上绝大多数抗焦虑、抗癫痫、镇静催眠药物（如安眠药）均是通过靶向不同的变构位点发挥作用的。之所以称为调节剂，意味着必须有GABA共存的情况下才能发挥作用，调节剂单独不产生任何作用。非选择性和选择性PAM 正变构调节剂包括非选择性和选择性PAM。一、非选择性PAM：常结合于GABAA受体经典的苯二氮䓬（BZ）结合位点，但不挑剔受体的亚型组合，会同时作用于多个包含a1、a2、a3或a5亚基的受体，包括：苯二氮䓬类（Benzodiazepines, BDZs）：如地西泮（Diazepam）、阿普唑仑（Alprazolam），结合于a与γ亚基交界面，能增加GABA与受体结合的频率，从而增强氯离子通道的开放频率。巴比妥类（Barbiturates）：如苯巴比妥，结合于通道内部或附近，延长氯离子通道的开放时间。神经活性类固醇：如阿法沙龙（Alfaxalone），结合于跨膜区，具有强大的镇静和麻醉作用。酒精（乙醇）：也是弱正变构调节剂，能增强GABAA受体活性。非选择性PAM优缺点：优点：广谱，起效快，在临床上是极佳的急救抗惊厥药、强效抗焦虑药和麻醉诱导剂。缺点/副作用：因为无差别激活，常伴随严重的“非靶点副作用”，如嗜睡、肌肉松弛过度导致的跌倒、认知和记忆力受损（作用于海马的受体），长期使用易产生耐受性和依赖性（成瘾）。二、选择性PAM：为了克服非选择性PAM引起的嗜睡、成瘾和记忆障碍，现代神经药理学致力于开发靶向特定a亚基亚型的PAM。 ①a1亚基选择性：代表药物：唑吡坦（Zolpidem）、扎来普隆（Zaleplon）。作用机制：优先作用于a1受体，专门用于镇静催眠。因为避开了其他亚型，理论上具有更纯粹的助眠效果，但长期服用仍有依赖性和停药有反弹风险。 ②a2/a3亚基选择性：代表药物：TPA023、Darigabat。作用机制：主要富集于杏仁核等控制情绪的脑区，高选择性增强 a2和a3亚基受体功能，这类药物是新一代无镇静作用的抗焦虑药的研发方向。 ③a5亚基选择性：代表药物：SH-053-2'F-R-CH3。作用机制：a5亚基主要分布在海马体，与认知和精神分裂症相关。选择性调控该亚基在精神疾病研究中展现出改善认知缺陷而不产生镇静作用的潜力。总结：非选择性PAMs（如苯二氮䓬类）代表了过去数十年经典镇静抗焦虑药，疗效确切但有“认知受损和成瘾”等硬伤。选择性PAMs（靶向a2或a3亚基）则是各大药企CNS管线中的新宠，力求实现“只抗焦虑/癫痫，不嗜睡也不损伤记忆”的精准医疗突破。寻医问诊，请扫上图的二维码，随时与我们沟通！往期相关文章，见链接抗癫痫药物发现史系列抗癫痫药物发现史系列一||人类历史上首个抗癫痫药物--溴化钾抗癫痫药物发现史系列二||偶然发现的抗癫痫药物--苯巴比妥抗癫痫药物发现史系列三||横空出世的史上最强抗癫痫药物--西诺氨酯抗癫痫药物百年演进：从偶然发现到精准治疗的未来图景

100 项与阿法沙龙相关的药物交易

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