在大鼠的自发精液排放上,α1 adrenoceptor对抗剂诱导的射精功能障碍的特征
Masaru Yoshizumi1, Shin-Nosuke Ise1, Akihiko Yonezawa2
1Division of Physiology and Anatomy, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
Basic & clinical pharmacology & toxicology
|February 27, 2024
概括
用于良性前列腺增生症的α1-adrenoceptor (α1-AR) 抗体可以导致射精障碍. 这项研究发现α1A-AR亚型主要负责这种副作用,主要是通过减少精液排放.
科学领域:
- 药理学 药理学是指药理学的学科.
- 泌尿器科 泌尿器科 泌尿器科 泌尿器科
- 神经科学是一个神经科学.
背景情况:
- 阿尔法1-上腺受体 (α1-AR) 抗剂通常用于良性前列腺增生症 (BPH).
- 射精障碍是这些药物的已知的不良影响,但它们的潜在机制仍然不清楚.
- 了解涉及的特定α1-AR亚型对于管理这些副作用至关重要.
研究的目的:
- 调查α1-AR抗体对α1-AR亚型有不同的亲和力对大鼠射精功能的影响.
- 阐明了α1-AR抗剂诱导的射精功能障碍背后的机制.
- 确定特定的α1-AR亚型在精液排放和射精中的作用.
主要方法:
- 在大鼠的自发精液排放 (SSE) 试验中,对α1-AR抗剂 (普拉佐辛,特拉佐辛,坦苏洛辛,纳夫托皮迪尔) 和选择性α1D-AR抗剂 (BMY7378) 进行全身治疗.
- 对药物对射精精质量的影响的剂量反应评估.
- 坦苏洛辛和纳夫托皮迪尔的静脉内给药,以评估中心与外围机制.
- 在慢性坦苏洛辛治疗后,评估精液囊液体体积和逆行性射精.
主要成果:
- 普拉佐辛,特拉佐辛,坦苏洛辛和纳夫托皮迪尔的全身药物剂量取决于排泄的精子物质的重量,其强度顺序为:坦苏洛辛 > 特拉佐辛 > 普拉佐辛 > 纳夫托皮迪尔.
- 选择性α1D-AR抗剂BMY7378对SSE没有影响.
- 内松素和纳夫托皮迪尔没有抑制SSE,这表明外围机制.
- 慢性松素治疗增加了精液囊液,但没有显著改变逆行性射精,表明精液排放的损失是功能障碍的主要原因.
结论:
- α1-AR对抗剂对自发精液排放的不同抑制功效主要归因于α1A-AR亚型的参与.
- 由α1-AR抗体诱导的射精功能障碍主要是由于周围水平的精液发射损失造成的.
- 虽然逆行性射精可能起到较小的作用,但主要机制涉及受损的精液排放,突出了α1A-AR对抗性的重要性.
相关概念视频
Adrenergic Antagonists: Pharmacological Actions of ɑ-Receptor Blockers
809
α-Adrenergic antagonists, known as α-blockers, exert their effects by inhibiting α-adrenoceptors, leading to specific physiological actions. α1-blockers and α2-blockers have distinct pharmacological actions and therapeutic applications.
α1-blockers: These drugs inhibit α1-adrenoceptors on smooth muscle cells, resulting in vasodilation. This vasodilation lowers blood pressure, making α1-blockers valuable in treating hypertension. Additionally,...
α1-blockers: These drugs inhibit α1-adrenoceptors on smooth muscle cells, resulting in vasodilation. This vasodilation lowers blood pressure, making α1-blockers valuable in treating hypertension. Additionally,...
809
Male Sexual Response: Erection & Ejaculation
2.3K
Sexual stimulation can take various forms, such as physical touch and visual or auditory cues. When this happens, the parasympathetic reflex in the sacral portion of the spinal cord is activated. This reflex stimulates the release of nitric oxide (NO), which then dilates the arterioles in the penis, increasing blood flow to the erectile tissues - the corpora cavernosa and corpus spongiosum.
The blood filling the erectile tissues compresses the veins, which helps to prevent blood from leaving...
The blood filling the erectile tissues compresses the veins, which helps to prevent blood from leaving...
2.3K
Adrenergic Receptors: ɑ Subtype
1.5K
Adrenoceptors are classified into α and ꞵ classes based on their potencies to catecholamine agonists. α-adrenoceptors show the following order of catecholamine potency:
Adrenaline ≥ Noradrenaline >> Isoprenaline
α-adrenoceptors are further divided into α1 and α2-adrenoceptors.
α1-Adrenoceptors: These receptors are located postsynaptically on the effector organs and cause constriction of smooth muscle mediated by activation of phospholipase...
Adrenaline ≥ Noradrenaline >> Isoprenaline
α-adrenoceptors are further divided into α1 and α2-adrenoceptors.
α1-Adrenoceptors: These receptors are located postsynaptically on the effector organs and cause constriction of smooth muscle mediated by activation of phospholipase...
1.5K
Adrenergic Antagonists: Chemistry and Classification of ɑ-Receptor Blockers
879
Adrenergic antagonists, or sympatholytics, inhibit adrenoceptor activation driven by catecholamines or agonists. Based on their adrenoceptor specificity, adrenergic blockers can be categorized into two primary groups: α-adrenergic blockers (α-blockers) and β-adrenergic blockers (β-blockers). α-blockers interact with α1 and α2 subtypes of α-adrenoceptors.
Nonselective α-blockers: Nonselective α-blockers contain haloalkylamine or imidazoline...
Nonselective α-blockers: Nonselective α-blockers contain haloalkylamine or imidazoline...
879
Adrenergic Agonists: Chemistry and Structure-Activity Relationship
3.0K
Adrenergic agonists' structure-activity relationship (SAR) determines their selectivity and efficacy. These agonists comprise a phenylethylamine moiety with an aromatic ring and an ethylamine side chain.
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of...
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of...
3.0K
Drugs Affecting Neurotransmitter Release or Uptake
1.1K
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...
1.1K


