mAChR

在冠状动脉平滑肌细胞中，奥昔布宁（0.1、0.3、1、3、10、30、100 μM；200 ms）以浓度依赖性方式抑制血管Kv通道，而不影响抗胆碱能作用[1]。

当 0.5 和 2 小时后发生特异性 [3H]N-甲基东莨菪碱结合时，奥昔布宁（27.2 mg/kg；口服；单次）显着结合小鼠脑部毒蕈碱受体，使 Kd 值增加约两倍[2]。

本研究证明了抗胆碱能药物奥昔布宁对兔冠状动脉平滑肌细胞电压依赖性K+（Kv）通道的抑制作用。奥昔布宁以浓度依赖的方式抑制血管Kv通道，IC50值为11.51±0.38μmol/L，Hill系数（n）为2.25±0.12。奥昔布宁的应用使活化曲线向右移动，失活曲线向左移动。Kv1.5亚型抑制剂DPO-1和Kv2.1亚型抑制剂广西毒素预处理抑制了奥昔布宁诱导的Kv电流抑制。然而，应用Kv7亚型抑制剂利诺哌啶不会影响奥昔布宁对Kv电流的抑制。抗胆碱能药物阿托品既不抑制Kv电流，也不影响奥昔布宁诱导的Kv电流抑制。根据这些结果，我们得出结论，奥昔布宁通过影响稳态激活和失活曲线，以浓度依赖的方式抑制血管Kv电流，而与其抗胆碱能作用无关[1]。

细胞活力测定[1]
细胞类型：冠状动脉平滑肌细胞（来自雄性新西兰白兔）
测试浓度： 10 μM
孵育时间： 200 ms
实验结果： 2分钟内快速抑制Kv电流，+60 Mv时Kv电流降低44%。通过改变 Kv 通道的门控特性来抑制 Kv 电流。

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细胞活力测定[1]
细胞类型：冠状动脉平滑肌细胞（来自雄性新西兰白兔）
测试浓度： > 0.1, 0.3, 1, 3, 10, 30, 100 μM
孵育时间： 200 ms
实验结果： 降低 Kv 电流幅度浓度依赖性，IC50值为11.51 μM。

Animal/Disease Models: Male ddY strain mice (9 to 13weeks old)[2].
Doses: 27.2 mg/kg (76.1 µmol/kg)
Route of Administration: Oral administration; single.
Experimental Results: Significant increased Kd values for specific [3H]NMS binding in Significant increased Kd values for specific [3H]NMS binding in mouse cerebral cortex with values of 120% and 71.2% when at 0.5 and 2 hrs (hours), respectively. .

Absorption, Distribution and Excretion
Oxybutynin should be swallowed whole with the help of liquids. A pharmacokinetic study revealed that oxybutynin was rapidly absorbed, and peak concentrations were reached within about 1 hour of administration, measured at 8.2 ngml-1 and AUC was 16 ngml-1. The biovailability of oxybutynin is about 6%, and the plasma concentration of the active metabolite, desethyloxybutynin is 5 to 12 times greater than that of oxybutynin. Bioavailability is increased in the elderly. Food has been shown to increase the exposure to controlled-release oxybutynin.
Oxybutynin is heavily cleared by the liver. Under 0.1% of an administered dose is found as unchanged drug in the urine. Less than 0.1% of a single dose of oxybutynin is excreted as desethyloxybutynin.
Oxybutynin has a wide volume of distribution of 193 L. In rats, oxybutynin penetrates the central nervous system.

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Metabolism / Metabolites
Oxybutynin is heavily metabolized by the CYP3A4 enzyme system in both the liver and the wall of the intestine. It undergoes first-pass metabolism, and its resulting primary active metabolite, N-desethyloxybutynin circulates. It is active at the muscarinic receptors in both the bladder and the salivary gland. Hepatic biotransformation also produces its major inactive metabolite, phenylcyclohexylglycolic acid.

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Biological Half-Life
The plasma elimination half-life is about 2 hours. In the elderly, the elimination half-life is prolonged up to 5 hours.

Hepatotoxicity
In multiple, large clinical trials of oxybutynin therapy for overactive bladder syndrome, serum enzyme elevations were rare and no more frequent than with placebo, and there were no episodes of clinically apparent liver injury. Since its approval and widespread use for more than four decades, there has been only a single published case of suspected liver injury attributed to oxybutynin – a report of transient serum enzyme elevations without jaundice or apparent symptoms in a patient with a severe ischemic stroke arising within weeks of starting oxybutynin. Thus, clinically apparent liver injury from oxybutynin is very rare if it occurs at all.
Likelihood score: E (unlikely cause of clinically apparent liver injury).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
No information is available on the use of oxybutynin during breastfeeding. Long-term use of oxybutynin might reduce milk production or milk letdown, but a single dose is not likely to interfere with breastfeeding. During long-term use, observe for signs of decreased lactation (e.g., insatiety, poor weight gain).
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Anticholinergics can inhibit lactation in animals, apparently by inhibiting growth hormone and oxytocin secretion. Anticholinergic drugs can also reduce serum prolactin in nonnursing women. The prolactin level in a mother with established lactation may not affect her ability to breastfeed. The manufacturer reports that cases of lactation suppression have been reported with some oxybutynin (immediate-release) formulations in postmarketing surveillance.

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Protein Binding
Oxybutynin enantiomers are more than 97% bound to plasma proteins, primarily to alpha-1 acid glycoprotein.

[1]. The anticholinergic drug oxybutynin inhibits voltage-dependent K+ channels in coronary arterial smooth muscle cells. Clin Exp Pharmacol Physiol. 2019 Nov;46(11):1030-1036.

[2]. Comparative evaluation of central muscarinic receptor binding activity by oxybutynin, tolterodine and darifenacin used to treat overactive bladder. J Urol. 2007 Feb;177(2):766-70.

Oxybutynin is a racemate comprising equimolar amounts of (R)-oxybutynin and esoxybutynin. An antispasmodic used for the treatment of overactive bladder. It has a role as a muscarinic antagonist, a muscle relaxant, an antispasmodic drug, a parasympatholytic, a calcium channel blocker and a local anaesthetic. It is a tertiary amino compound and a racemate. It contains an esoxybutynin and a (R)-oxybutynin.
Overactive bladder (OAB) is a common condition negatively impacting the lives of millions of patients worldwide. Due to its urinary symptoms that include nocturia, urgency, and frequency, this condition causes social embarrassment and a poor quality of life. Oxybutynin, also marketed as Ditropan XL, is an anticholinergic medication used for the relief of overactive bladder symptoms that has been optimized for high levels of safety and efficacy since initial FDA approval in 1975. This drug relieves undesirable urinary symptoms, increasing the quality of life for patients affected by OAB. It is often used as first-line therapy for OAB.
Oxybutynin is a Cholinergic Muscarinic Antagonist. The mechanism of action of oxybutynin is as a Cholinergic Muscarinic Antagonist.
Oxybutynin is a synthetic anticholinergic agent that is used for treatment of urinary incontinence and overactive bladder syndrome. Oxybutynin has not been implicated in causing liver enzyme elevations or clinically apparent acute liver injury.
Oxybutynin is a tertiary amine possessing antimuscarinic and antispasmodic properties. Oxybutynin blocks muscarinic receptors in smooth muscle, hence inhibiting acetylcholine binding and subsequent reduction of involuntary muscle contractions. Oxybutynin is used to reduce bladder contractions by relaxing bladder smooth muscle.
See also: Oxybutynin Chloride (has salt form).

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Drug Indication
Oxybutynin is indicated for the symptomatic treatment of overactive bladder, which causes urge urinary incontinence and frequency, and urgency. Oxybutynin may also be used for children aged 6 and above for the symptomatic management of detrusor muscle overactivity which has been found to be related to a neurological condition. Spina bifida is an example of a neurological condition in which oxybutynin may be used to control urinary symptoms. On occasion, oxybutynin may be used off-label to relieve bladder spasms associated with ureteral stents or urinary catheters.
Symptomatic treatment of urge incontinence and/or increased urinary frequency and urgency as may occur in adult patients with unstable bladder.

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Mechanism of Action
Oxybutynin acts to relax the bladder by inhibiting the muscarinic action of acetylcholine on smooth muscle, and not skeletal muscle. The active of oxybutynin is metabolite is N-desethyloxybutynin. It competitively inhibits the postganglionic type 1, 2 and 3 muscarinic receptors. The above actions lead to increased urine capacity in the bladder, decreasing urinary urgency and frequency. In addition, oxybutynin delays the initial desire to void.
RESULTS OF CYSTOMETRIC STUDIES SHOWED THAT THE DRUG INCR BLADDER CAPACITY @ ONSET OF FIRST CONTRACTION & FIRST DESIRE TO VOID, AS WELL AS @ END OF CYSTOMETRY. /CHLORIDE/

C22H31NO3

357.49

357.23

C, 73.92; H, 8.74; N, 3.92; O, 13.43

5633-20-5

Oxybutynin;5633-20-5;Oxybutynin chloride;1508-65-2;(R)-Oxybutynin hydrochloride;1207344-05-5;Oxybutynin-d11 chloride;1185151-95-4; Oxybutynin;5633-20-5;(R)-Oxybutynin hydrochloride;1207344-05-5;Oxybutynin-d11 chloride;1185151-95-4;(R)-Oxybutynin;119618-21-2; 5633-20-5 (racemate); 1508-65-2 (racemate HCl); 1207344-05-5 (R-isomer HCl); 119618-21-2 (R-isomer); 2738613-22-2 (R-isomer citrate); 119618-22-3 (S-isomer); 2862851-81-6 (R-isomer tartrate); 230949-16-3 (S-isomer HCl)

4634

Typically exists as White to off-white solids at room temperature

1.1±0.1 g/cm3

494.4±45.0 °C at 760 mmHg

125 - 130ºC

252.8±28.7 °C

0.0±1.3 mmHg at 25°C

1.546

5.19

49.77

1

4

8

26

490

0

O([H])C(C(=O)OC([H])([H])C#CC([H])([H])N(C([H])([H])C([H])([H])[H])C([H])([H])C([H])([H])[H])(C1C([H])=C([H])C([H])=C([H])C=1[H])C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H]

XIQVNETUBQGFHX-UHFFFAOYSA-N

InChI=1S/C22H31NO3/c1-3-23(4-2)17-11-12-18-26-21(24)22(25,19-13-7-5-8-14-19)20-15-9-6-10-16-20/h5,7-8,13-14,20,25H,3-4,6,9-10,15-18H2,1-2H3

4-(diethylamino)but-2-ynyl 2-cyclohexyl-2-hydroxy-2-phenylacetate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

配方 1 中的溶解度: 2.08 mg/mL (5.82 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 悬浮液；超声助溶。
例如，若需制备1 mL的工作液，可将100 μL 20.8 mg/mL澄清DMSO储备液加入400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.08 mg/mL (5.82 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 20.8 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.08 mg/mL (5.82 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 20.8 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。