Bykov Vladimir, Gushchina Evgenia, Morozov Sergey, Zhuravskaya Natalia, Kryshen Kirill, Makarov Valery, Matichin Aleksandr, Zueva Alena
N.N. Petrov National Medical Research Center of Oncology, Saint Petersburg, Russia.
PIQ-PHARMA LLC, Oruzheyniy pereulok, Moscow, Russia.
Sex Med. 2022 Feb;10(1):100477. doi: 10.1016/j.esxm.2021.100477. Epub 2022 Jan 8.
Management of diabetes mellitus-induced erectile dysfunction (DMED) is challenging because of its insufficient responses to phosphodiesterase type 5 inhibitors.
To compare the effects of ipidacrine, a reversible cholinesterase inhibitor, and sildenafil on DMED in a rat model of streptozotocin (STZ)-induced diabetes.
Erectile dysfunction (ED) caused by STZ-induced diabetes mellitus was modeled in adult male Wistar rats, which were randomized to 4 groups: untreated diabetic rats, sildenafil (5 mg/kg), ipidacrine (3.6 mg/kg) and ipidacrine (6.7 mg/kg). The test drug (ipidacrine), comparator (sildenafil) or control substance (1% starch solution) were administered orally for 5 days or 14 days. Erectile function was assessed by the change in the maximum intracavernous pressure (ICPmax) following cavernous nerve electrical stimulation. The mean arterial pressure (MAP) was recorded, and the ICPmax/MAP ratio was calculated. Sexual behavior, cholinesterase activity and blood testosterone level tests assessed.
The quantitative value of ICPmax/MAP 14 days after the start of administration of the test drug and the comparison drug.
Animals with STZ-induced diabetes mellitus showed a significant decrease in ICPmax and ICPmax/MAP ratio compared to the intact control group. When ipidacrine was administered to rats with DMED for 14 days, an increase in these indicators was noted. It was proved that ipidacrine at a dose of 6.7 mg/kg has noninferiority compared to sildenafil on the DMED model. Significant increase in ICPmax compared to STZ-control after electrostimulation of the cavernous nerve was recorded following administration of ipidacrine at a dose of 6.7 mg/kg (P < .05) and sildenafil at a dose 5 mg/kg (P < .05). Neither the test drug, nor the comparator were associated with increase in testosterone levels in blood; as well both drugs did not promote activation of sexual behavior.
Ipidacrine may be considered as an effective therapy for DMED but needs to be verified in human investigations.
STRENGTHS & LIMITATIONS: The role of ipidacrine, was firstly demonstrated in rats with DMED. However, the results were obtained in animal experiments, and will be further tested in the study of receptor interactions and the determination of cellular targets.
This is the first study to show that administration of ipidacrine, the reversible cholinesterase inhibitor, improved erectile function in diabetic rats and these results may be beneficial in further studies using ipidacrine for treatment of DMED, particularly in non-responders to PDE5 inhibitors. Bykov V, Gushchina E, Morozov S, et al. Ipidacrine (Axamon), A Reversible Cholinesterase Inhibitor, Improves Erectile Function in Male Rats With Diabetes Mellitus-Induced Erectile Dysfunction. Sex Med 2022;10:100477.
糖尿病性勃起功能障碍（DMED）的治疗具有挑战性，因为其对5型磷酸二酯酶抑制剂反应不足。
在链脲佐菌素（STZ）诱导的糖尿病大鼠模型中，比较可逆性胆碱酯酶抑制剂茚达卡林和西地那非对DMED的影响。
在成年雄性Wistar大鼠中建立STZ诱导的糖尿病性勃起功能障碍（ED）模型，将其随机分为4组：未治疗的糖尿病大鼠、西地那非（5mg/kg）、茚达卡林（3.6mg/kg）和茚达卡林（6.7mg/kg）。口服给予受试药物（茚达卡林）、对照药物（西地那非）或对照物质（1%淀粉溶液），持续5天或14天。通过海绵体神经电刺激后最大海绵体内压（ICPmax）的变化评估勃起功能。记录平均动脉压（MAP），并计算ICPmax/MAP比值。进行性行为、胆碱酯酶活性和血睾酮水平检测。
受试药物和对照药物给药14天后ICPmax/MAP的定量值及比较。
与完整对照组相比，STZ诱导的糖尿病动物的ICPmax和ICPmax/MAP比值显著降低。给DMED大鼠服用茚达卡林14天后，这些指标有所增加。结果证明，在DMED模型中，6.7mg/kg剂量的茚达卡林与西地那非相比具有非劣效性。给予6.7mg/kg剂量的茚达卡林（P<.05）和5mg/kg剂量的西地那非（P<.05）后，海绵体神经电刺激后记录到的ICPmax与STZ对照组相比显著增加。受试药物和对照药物均未使血睾酮水平升高；两种药物也均未促进性行为激活。
茚达卡林可被视为DMED的有效治疗方法，但需要在人体研究中进行验证。
茚达卡林在DMED大鼠中的作用首次得到证实。然而，这些结果是在动物实验中获得的，将在受体相互作用研究和细胞靶点确定中进一步测试。
这是第一项表明给予可逆性胆碱酯酶抑制剂茚达卡林可改善糖尿病大鼠勃起功能的研究，这些结果可能有助于进一步研究使用茚达卡林治疗DMED，特别是对PDE5抑制剂无反应者。Bykov V, Gushchina E, Morozov S等。茚达卡林（Axamon），一种可逆性胆碱酯酶抑制剂，可改善糖尿病性勃起功能障碍雄性大鼠的勃起功能。性医学2022；10：100477。
