846. Vesicular monoamine transport inhibitors: current uses and future directions.
Advancements over the past decade in understanding vesicular monoamine transporter 2 (VMAT2) inhibitors highlight their key role in the treatment of movement and neuropsychiatric disorders. VMAT2 is crucial for packaging neurotransmitters such as serotonin, dopamine, and norepinephrine into synaptic vesicles, facilitating their release and reuptake in synaptic transmission. VMAT2 inhibitors, such as tetrabenazine, deutetrabenazine, and valbenazine, show therapeutic efficacy in managing hyperkinetic movement disorders, including Huntington's disease, tardive dyskinesia, and Tourette's syndrome. These inhibitors modulate excessive synaptic activity by reducing neurotransmitter storage and release. Genetic variations, particularly in the cytochrome P450 enzyme family, influence VMAT2 inhibitor metabolism, necessitating personalised dosing to optimise efficacy and minimise adverse events. Recent studies have provided further structural insights into VMAT2 inhibition mechanisms, paving the way for the development of inhibitors with enhanced potency and selectivity. Leveraging pharmacogenetics for precision medicine and exploring VMAT2 inhibition in broader therapeutic contexts could revolutionise treatment frameworks for neurological and psychiatric conditions.
847. Post-exposure prophylaxis regimen of rabies monoclonal antibody and vaccine in category 3 potential exposure patients: a phase 4, open-label, randomised, active-controlled trial.
作者: Prasad S Kulkarni.;Anirudha Vyankatesh Potey.;Dhananjay Kapse.;Chetanraj Bhamare.;Avinash Gawande.;Renuka Munshi.;Sudhir Pawar.;Nithya J Gogtay.;Anurag Agarwal.;Muralidhar Tambe.;Sushama Thakre.;Clarence J Samuel.;Shahzada Mohmed Salim Khan.;Ravish H S.;Devang Rana.;Neha Singh.;Veena Kamath.;Hira Lal Bhalla.;Cyrus S Poonawalla.;Reeta S Mani.;Bhagwat Gunale.; .
来源: Lancet. 2025年406卷10503期627-635页
Rabies is almost invariably fatal. A rabies monoclonal antibody (RmAb) was approved in India in 2016 for passive prophylaxis. This post-marketing study aimed to evaluate the long-term safety, immunogenicity, and efficacy of a post-exposure prophylaxis (PEP) regimen containing RmAb.
848. Adagrasib versus docetaxel in KRASG12C-mutated non-small-cell lung cancer (KRYSTAL-12): a randomised, open-label, phase 3 trial.
作者: Fabrice Barlesi.;Wenxiu Yao.;Michaël Duruisseaux.;Ludovic Doucet.;Aitor Azkárate Martínez.;Vanesa Gregorc.;Oscar Juan-Vidal.;Shun Lu.;Charlotte De Bondt.;Filippo de Marinis.;Helena Linardou.;Young-Chul Kim.;Robert Jotte.;Enriqueta Felip.;Giuseppe Lo Russo.;Martin Reck.;Mary F Michenzie.;Wenjing Yang.;Julie N Meade.;Beata Korytowsky.;Tony S K Mok.; .
来源: Lancet. 2025年406卷10503期615-626页
Adagrasib is a KRASG12C inhibitor that demonstrated promising activity against KRASG12C-mutated advanced non-small-cell lung cancer (NSCLC) in a phase 2 trial. Here we aimed to compare the efficacy and safety of adagrasib versus docetaxel in patients with KRASG12C-mutated advanced NSCLC previously treated with chemotherapy and immunotherapy.
849. Extending the duration of endocrine treatment for early breast cancer: patient-level meta-analysis of 12 randomised trials of aromatase inhibitors in 22 031 postmenopausal women already treated with at least 5 years of endocrine therapy.
In postmenopausal women with oestrogen receptor-positive early breast cancer, 5 years of adjuvant tamoxifen substantially reduces 15-year recurrence and mortality; aromatase inhibitor treatment (AIT) is even more effective. We assess the effects of further AIT among women recurrence-free after at least 5 years of endocrine therapy.
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