在糖尿病组的海绵体条中，阿伐那非 (TA-1790) (0.01-1000 µM) 可使电场刺激 (1-20 Hz) 引起的松弛反应增加 45%[2]。

Avanafil (TA-1790)（10 mg/kg；口服；每日，持续 30 天；雄性大鼠）可显着减少地塞米松引起的氧化应激、骨萎缩和 BMD 损失，同时通过激活 NO 增加骨组织中的血管生成、cGMP 和 PKG (NO/cGMP/PKG) 信号通路[1]。阿伐那非 (TA-1790)（10 µM；ICI；一次，持续 10 周）可改善 T2DM 大鼠的勃起反应[2]。

Animal/Disease Models: Male rat model of glucocorticoid-induced osteoporosis (GIOP)[1]
Doses: 10 mg/kg
Route of Administration: Oral administration; daily, for 30 days
Experimental Results: diminished the level of eNOS, NO, PDE-5, PICP, MDA, CoQ10/CoQ10H and 8-OHdG/108dG. Increased the level of cGMP, PKG, Cortisol and CTCP.

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Animal/Disease Models: Male rat model of glucocorticoid-induced osteoporosis (GIOP)[1]
Doses: 10 mg/kg
Route of Administration: Oral administration; daily, for 30 days
Experimental Results: Increased right femur trabecular bone thickness and epiphyseal bone width.

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Animal/Disease Models: Male T2DM Sprague Dawley rats[2]
Doses: 10 µM
Route of Administration: Intracavernous injection; once, for 10 weeks
Experimental Results: Increased in ICP/MAP in response to nerve stimulation and increased total ICP values.

Absorption, Distribution and Excretion
Avanafil is rapidly absorbed following oral administration (Tmax of 30-45 minutes) and appears to have low to moderate oral bioavailability, though formal studies have not been conducted. Administration with a meal results in a mean delay in Tmax of 1.12 to 1.25 hours, a 39% mean reduction in Cmax, and a negligible effect on AUC.
Following oral administration, avanafil is extensively metabolized. Approximately 62% of a given dose is excreted as metabolites in the feces and approximately 21% as metabolites in the urine.
The apparent volume of distribution of avanafil is 47 to 83 L.

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Metabolism / Metabolites
Avanafil is extensively metabolized, primarily by CYP3A4 and to a lesser extent by CYP2C9. There are two major metabolites formed, M4 and M16, which exist in the plasma at concentrations 23% and 29% that of the parent compound, respectively. The M16 metabolite lacks pharmacologic effect, but the M4 metabolite has an inhibitory potency for PDE5 18% that of avanafil and accounts for approximately 4% of the observed pharmacologic activity of avanafil.

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Biological Half-Life
Studies have demonstrated variability in the terminal elimination half-life of avanafil, with estimates ranging between 5 - 17 hours.

Hepatotoxicity
Avanafil has had limited general use, but in premarketing studies it was not associated with cases of clinically apparent liver injury and serum enzyme elevations were not reported. The related PDE5 inhibitors, sildenafil and tadalafil, have been linked to isolated, rare instances of acute liver injury and jaundice. The latency to onset ranged from a few days to 3 months and the pattern of injury was usually cholestatic. Autoimmune and immunoallergic features were not observed and all cases were self-limited without residual injury or acute liver failure. Whether avanafil can cause a similar form of acute liver injury is not yet known.
Likelihood score: E* (unproved but suspected rare cause of clinically apparent liver injury).

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Protein Binding
Avanafil and its two major metabolites, M4 and M16, are highly protein-bound in plasma at approximately 99%, 97%, and 81%, respectively. Binding occurs primarily to albumin (99%), with smaller contributions from γ-globulin (43%) and α1-acid glycoprotein (66%).

[1]. Effects of the Phosphodiesterase-5 (PDE-5) Inhibitors, Avanafil and Zaprinast, on Bone Remodeling and Oxidative Damage in a Rat Model of Glucocorticoid-Induced Osteoporosis. Med Sci Monit Basic Res. 2018 Mar 13;24:47-58.

[2]. The effect of intracavernosal avanafil, a newer phosphodiesterase-5 inhibitor, on neonatal type 2 diabetic rats with erectile dysfunction. Urology. 2014 Feb;83(2):508.e7-12.

[3]. Avanafil, a potent and highly selective phosphodiesterase-5 inhibitor for erectile dysfunction. J Urol. 2012 Aug;188(2):668-74.

Avanafil is a monocarboxylic acid amide obtained by formal condensation of the carboxy group of 4-[(3-chloro-4-methoxybenzyl)amino]-2-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]pyrimidine-5-carboxylic acid with the amino group of pyrimidin-2-ylmethylamine. Used for treatment of erectile dysfunction. It has a role as an EC 3.1.4.* (phosphoric diester hydrolase) inhibitor and a vasodilator agent. It is a member of pyrimidines, an aromatic amide, an organochlorine compound, a member of prolinols and a monocarboxylic acid amide.
Avanafil is a phosphodiesterase-5 (PDE5) inhibitor used in the treatment of erectile dysfunction. In comparison with other drugs of the same class, it shows greater selectivity for PDE5 over PDE6 than both [sildenafil] and [vardenafil] but less selectivity than [tadalafil], suggesting a relatively lower risk of visual disturbances associated with off-target PDE6 inhibition. It first received FDA approval on April 27, 2012, with subsequent EMA approval in June 2013.
Avanafil is a Phosphodiesterase 5 Inhibitor. The mechanism of action of avanafil is as a Phosphodiesterase 5 Inhibitor.
Avanafil is a selective inhibitor of phosphodiesterase type 5 (PDE5) and is used as therapy of erectile dysfunction. Avanafil is a relatively new medication and has yet to be linked to instances of serum enzyme elevations or with clinically apparent acute liver injury.
Avanafil is an orally available phosphodiesterase type 5 (PDE5) inhibitor with vasodilatory activity. Avanafil selectively inhibits PDE5, thus inhibiting the degradation of cyclic guanosine monophosphate (cGMP) found in the smooth muscle of the corpus cavernosa of the penis. The inhibition of cGMP degradation results in prolonged muscle relaxation, vasodilation, and blood engorgement of the corpus cavernosa, thereby prolonging penile erection.

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Drug Indication
Avanafil is indicated for the treatment of erectile dysfunction.
FDA Label
Treatment of erectile dysfunction in adult men. In order for Spedra to be effective, sexual stimulation is required.

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Mechanism of Action
Avanafil inhibits the cGMP-specific phosphodiesterase type 5 (PDE5) which is responsible for the degradation of cGMP in the corpus cavernosum located around the penis. Sexual arousal results in the local release of nitric oxide, which in turn stimulates the enzyme guanylate cyclase to produce cGMP. Elevated levels of cGMP result in local smooth muscle relaxation and increased blood flow to the penis (i.e. an erection). As PDE5 inhibitors like avanafil require the endogenous release of nitric oxide in order to exert their pharmacologic effect, they have no effect on the user in the absence of sexual stimulation/arousal.

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Pharmacodynamics
Avanafil is a strong competitive inhibitor of phosphodiesterase 5 (PDE5) with a demonstrated _in vitro_ IC₅₀ of 5.2 nM. Its inhibitory effects on PDE5 are 100-fold more potent than on PDE6 and >1000-fold more potent than on other PDE enzymes, meaning it is less likely to cause visual disturbances and cardiovascular adverse effects when compared with less selective PDE5 inhibitors such as [sildenafil] and [vardenafil]. It has a relatively quick onset of action allowing for administration as early as 15 minutes prior to sexual activity. PDE5 inhibitors like avanafil can cause significant drug interactions when administered alongside certain antihypertensive agents (e.g. alpha blockers, substantial amounts of alcohol). PDE5 inhibitors have also been associated with the development of non-arteritic anterior ischemic optic neuropathy (NAION), a rare condition that typically presents as sudden loss of vision in one or both eyes and appears to be more common in patients with a "crowded" optic disc. Patients presenting with any degree of vision loss should immediately discontinue use of all PDE5 inhibitors and seek medical attention. In some jurisdictions, a history of NAION or other degenerative retinal disorders is considered a contraindication to avanafil therapy.

C23H26CLN7O3

483.95

483.178

330784-47-9

Avanafil dibenzenesulfonate;330784-48-0;(R)-Avanafil;1638497-26-3;Avanafil-13C,d3

9869929

White to off-white solid powder

1.4±0.1 g/cm3

150-152ºC

1.651

3.52

125.39

3

9

9

34

642

1

COC1=C(C=C(C=C1)CNC2=NC(=NC=C2C(=O)NCC3=NC=CC=N3)N4CCC[C@H]4CO)Cl

WEAJZXNPAWBCOA-INIZCTEOSA-N

InChI=1S/C23H26ClN7O3/c1-34-19-6-5-15(10-18(19)24)11-27-21-17(22(33)28-13-20-25-7-3-8-26-20)12-29-23(30-21)31-9-2-4-16(31)14-32/h3,5-8,10,12,16,32H,2,4,9,11,13-14H2,1H3,(H,28,33)(H,27,29,30)/t16-/m0/s1

(S)-4-[(3-Chloro-4-methoxybenzyl)amino]-2-[2-(hydroxymethyl)-1-pyrrolidinyl]-N-(2pyrimidinylmethyl)-5-pyrimidinecarboxamide

TA 1790; TA1790; Avanafil; TA-1790; trade name: Stendra; Spedra

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: ≥ 2.5 mg/mL (5.17 mM) (饱和度未知) 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), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到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: ≥ 2.5 mg/mL (5.17 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 25.0 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: ≥ 2.5 mg/mL (5.17 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 25.0 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。