机器学习工具,用于新的选择性色胺和色胺 - 上腺素再吸收抑制剂
Natalia Łapińska1, Jakub Szlęk1,2, Adam Pacławski1
1Department of Pharmaceutical Technology and Biopharmaceutics, Jagiellonian University Medical College, 30-688 Kraków, Poland.
Molecules (Basel, Switzerland)
|February 13, 2025
概括
研究人员开发了对血清素和上腺素载体的定量结构-活性关系 (QSAR) 模型,以预测抗抑郁药物潜在作用. 这些新的QSAR模型增强了治疗抑郁症的新分子的发现.
科学领域:
- 药用化学 医学化学
- 计算化学计算化学
- 药理学 药理学是指药理学的学科.
背景情况:
- 抑郁症影响大约5%的人口,选择性血清素再吸收抑制剂 (SSRI) 和血清素-上腺素再吸收抑制剂 (SNRIs) 作为一线治疗方法.
- 开发新型抗抑郁药需要预测新化学实体对血清素 (SERT) 和上腺素 (NET) 载体的亲和力和抑制潜力.
研究的目的:
- 为SERT和NET运输商开发强大的定量结构-活动关系 (QSAR) 模型.
- 预测针对SERT和NET的新型分子的亲和力 (pIC50) 和抑制潜力 (pKi).
主要方法:
- 使用自动机器学习工具Mljar.使用QSAR模型进行了构建.
- 两个维的Mordred描述符被用于分子表示.
- 模型对80%的数据进行了训练,并进行了10倍的交叉验证,对剩余20%的数据进行了外部验证.
主要成果:
- 经过验证的QSAR模型证明了SERT和NET传送器的预测能力.
- 对于NET,R平方值达到0.640 (pIC50) 和0.709 (pKi).
- 对于SERT,R平方值达到了0.678 (pIC50) 和0.828 (pKi).
结论:
- 开发的QSAR模型为SERT和NET传送器相互作用提供了可靠的预测.
- 这些模型被集成到氨酸AI应用程序中,促进了对抑郁症的药物发现.
相关概念视频
Antidepressant Drugs: MAOIs and Other Agents
183
Atypical antidepressants, including bupropion (Wellbutrin), mirtazapine (Remeron), nefazodone (Serzone), trazodone (Desyrel), and vilazodone (Viibryd), offer unique mechanisms of action. Bupropion weakly inhibits dopamine and norepinephrine reuptake, aiding depression treatment and smoking cessation, with a low risk of sexual dysfunction. Mirtazapine enhances serotonin and norepinephrine neurotransmission, leading to sedation, increased appetite, and weight gain. As a result, it helps treat...
183
Antidepressant Drugs: Tricyclics, SSRIs, and SNRIs
285
Tricyclic Antidepressants (TCAs), including Desipramine (Norpramin), Imipramine (Tofranil), Clomipramine (Anafranil), and Amitriptyline (Elavil), inhibit serotonin and norepinephrine reuptake and also block other receptors. They are used for depression, pain conditions, and insomnia. Common adverse effects include anticholinergic effects, sedation, orthostatic hypotension, and weight gain. They have a narrow therapeutic window and so require plasma-level monitoring. Abrupt discontinuation can...
285
Drugs Affecting Neurotransmitter Release or Uptake
928
Certain drugs can affect how neurotransmitters called catecholamines, are released or taken back up in the adrenergic neuron. They can have different effects on the body's sympathetic transmission. Reserpine, a natural compound found in the Rauwolfia shrub, blocks a transporter called vesicular monoamine transporter (VMAT), which leads to a buildup of catecholamines in the cell and reduces sympathetic transmission. Another drug called guanethidine works in multiple ways, including blocking...
928
Antidepressant Drugs: Overview
351
Antidepressant drugs are a class of medications primarily used for treating various mood disorders, including major depression, anxiety disorders, and other related conditions. These medicines work by modulating the neurotransmitter balance within the brain, alleviating depressive symptoms. Antidepressants can be broadly categorized into several groups according to their mechanism of action and chemical structure: Selective Serotonin Reuptake Inhibitors (SSRIs), Serotonin-Norepinephrine...
351
Drugs Affecting GI Tract Motility: Serotonin Receptor Agonists
204
Serotonin, a crucial neurotransmitter synthesized by enterochromaffin cells, plays a cardinal role in regulating gastrointestinal (GI) motility. With over 90% of the body's total serotonin in the GI tract, its influence on digestive processes is profound. Serotonin is swiftly released upon various stimuli, such as food boluses or certain drugs, triggering intrinsic sensory neurons in the myenteric plexus and extrinsic vagal and spinal sensory neurons. This leads to the activation of the...
204
Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance
72
The elimination half-life and drug clearance of drugs following nonlinear kinetics can vary with dosage. The Michaelis-Menten parameters and drug concentration influence these factors. As the dose increases, the elimination half-life tends to lengthen, resulting in a reduction in clearance and a disproportionately larger area under the curve. The total clearance can be derived from the Michaelis-Menten equation for drugs following a one-compartment model.
A study on guinea pigs examined the...
A study on guinea pigs examined the...
72


