Melanocortin receptors: MC1R, MC4R, MC3R, MC5R, and MC2R

布美拉肽是一种多种黑皮质素受体的激动剂，按其效力强弱依次为MC1R、MC4R、MC3R、MC5R和MC2R。目前尚不清楚激动这些受体如何改善性欲减退障碍，但MC4R受体广泛存在于中枢神经系统的多个区域。MC3R和MC4R分布于下丘脑，参与食物摄入和能量稳态调节。一种理论认为，布美拉肽刺激内侧视前区的多巴胺释放，该区域与多种生物的性行为相关。 布美拉肽是一种黑皮质素受体激动剂，需在预期性行为前45分钟注射使用。激动黑皮质素受体MC1R也会导致黑色素表达增加。

布美拉肽 是一种由7个氨基酸组成的多肽，用于治疗绝经前女性的性欲减退障碍。布美拉肽与酒精无相互作用。目前，其作用于受体的机制如何转化为临床疗效尚不明确。该药物首次在文献中被描述是在2003年，当时的研发代号为PT-141。此后，针对其治疗男女性功能障碍的潜力进行了研究，但目前仅获批用于女性。其他用于治疗女性性功能障碍的药物包括[氟班色林]、[雌激素]、[奥培米芬] 和 [普拉睾酮]。布美拉肽于2019年6月21日获得美国食品药品监督管理局批准。 布美拉肽是一种黑皮质素受体激动剂，其作用机制即基于此特性。 作为一种通过注射给药的黑皮质素受体激动剂，布美拉肽用于治疗女性性欲减退障碍。据报道，布美拉肽在治疗期间可能导致轻微的血清转氨酶升高，并与少数临床明显的急性肝损伤病例有关。 布美拉肽 是一种蛋白质类药物，其最高临床试验阶段（在所有适应症中）为IV期，于2019年首次获批，目前拥有3个已获批适应症和3个研究中的适应症。

Absorption, Distribution and Excretion
The Tmax of bremelanotide is 1.0 h (0.5–1.0 h), with a bioavailability of 100%. The Cmax is 72.8 ng/mL, and the AUC is 276 hng/mL. 64.8% of the radiolabeled dose is excreted in the urine, and 22.8% is recovered in the feces. The mean volume of distribution of bremelanotide is 25.0 ± 5.8 L. The mean clearance of bremelanotide is 6.5 ± 1.0 L/h. Metabolism/Metabolites Bremelanotide consists of 7 amino acids, therefore its metabolism involves multiple hydrolytic reactions. Biological Half-Life The half-life of bremelanotide is 2.7 h (1.9–4.0 h).

Hepatotoxicity
In pre-registration clinical trials, a small number of patients treated with bumeranolide reported elevated serum enzymes, a similar proportion of which occurred in the placebo group. One patient who received 10 bumeranolide injections within one year developed acute hepatitis, characterized by significantly elevated serum transaminase levels, mildly elevated alkaline phosphatase, and mild jaundice; symptoms resolved upon discontinuation of the drug. There are currently no reported cases of bumeranolide causing acute liver failure or chronic liver injury, but overall clinical experience with this drug is limited. Therefore, bumeranolide may cause acute liver injury, but this is rare. Probability score: D (likely a rare cause of clinically significant liver injury). Pregnancy and Lactation Effects ◉ Overview of Use During Lactation There is currently no information on the clinical use of bumeranolide during lactation. Because bumelanopeptide is a cyclic peptide molecule with a molecular weight of 1025, its content in breast milk is likely to be very low, and it is unlikely to be absorbed because it may be destroyed in the infant's gastrointestinal tract. Until more data are available, breastfeeding women should use bumelanopeptide with caution, especially when breastfeeding newborns or premature infants.
◉ Effects on breastfed infants
No published information found as of the revision date.
◉ Effects on lactation and breast milk
No published information found as of the revision date.

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Protein binding
Bumelanopeptide has a protein binding rate of 21% in serum.

[1]. Bremelanotide: an overview of preclinical CNS effects on female sexual function. J Sex Med. 2007 Nov;4 Suppl 4:269-79.

[2]. PT-141: a melanocortin agonist for the treatment of sexual dysfunction. Ann N Y Acad Sci. 2003 Jun;994:96-102.

Bumelanotide is an oligopeptide. It is a 7-amino acid peptide used to treat hypoactive sexual desire disorder in premenopausal women. Bumelanotide does not interact with alcohol. The mechanism by which bumelanotide acts on receptors to produce clinical efficacy is not fully understood. Bumelanotide was first reported in the literature in 2003 under the research code PT-141. Since then, its use in treating male and female sexual dysfunction has been investigated, but it is currently only approved for use in women. Other medications used to treat female sexual dysfunction include flubanoxetine, estrogen, opemifene, and prastorhinone. Bumelanotide received approval from the U.S. Food and Drug Administration (FDA) on June 21, 2019. Bumelanotide is a melanocortin receptor agonist. Its mechanism of action is as a melanocortin receptor agonist. Bumelanotide is a parenteral melanocortin receptor agonist used to treat hypoactive sexual desire disorder in women. Bumeranolide has been reported to cause mild elevation of serum enzymes during treatment and has been associated with rare cases of clinically significant acute liver injury. See also: Bumeranolide acetate (active ingredient). Drug Indications Bumeranolide is indicated for the treatment of hypoactive sexual desire disorder in premenopausal women not caused by medical or psychiatric illness, partner problems, or drug side effects. Mechanism of Action Bumeranolide is an agonist of multiple melanocortin receptors, in order of potency: MC1R, MC4R, MC3R, MC5R, and MC2R. It is currently unclear how these receptor agonists improve hypoactive sexual desire disorder, but the MC4R receptor is present in many areas of the central nervous system. MC3R and MC4R are present in the hypothalamus and are involved in food intake and energy homeostasis. One theory suggests that bumeranolide stimulates the release of dopamine in the medial preoptic area, which is involved in sexual behavior in various organisms.

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Pharmacodynamics
Bumelanotide is a melanocortin receptor agonist, administered 45 minutes before anticipated sexual activity. Agonism of the melanocortin receptor MC1R also leads to increased melanin expression. Nausea, headache, and vomiting may also occur in patients taking bumelanotide.

C50H68N14O10

1025.18

1024.524

C, 58.58; H, 6.69; N, 19.13; O, 15.61

189691-06-3

Bremelanotide Acetate; 1607799-13-2

9941379

Nle-D(1)HFRWK(1); Ac-Nle-Asp(1)-His-D-Phe-Arg-Trp-Lys(1)-OH

XDHFRWK

Solid powder

1.4±0.1 g/cm3

1.679

-1.21

376.47

13

12

17

74

1950

7

CCCC[C@H](NC(C)=O)C(N[C@H]1CC(NCCCC[C@H](NC([C@@H](NC([C@@H](NC([C@H](NC([C@@H](NC1=O)CC2=CN=CN2)=O)CC3=CC=CC=C3)=O)CCCNC(N)=N)=O)CC4=CNC5=CC=CC=C45)=O)C(O)=O)=O)=O

FFHBJDQSGDNCIV-MFVUMRCOSA-N

InChI=1S/C50H68N14O10/c1-3-4-16-35(58-29(2)65)43(67)64-41-25-42(66)54-20-11-10-18-37(49(73)74)60-46(70)39(23-31-26-56-34-17-9-8-15-33(31)34)62-44(68)36(19-12-21-55-50(51)52)59-45(69)38(22-30-13-6-5-7-14-30)61-47(71)40(63-48(41)72)24-32-27-53-28-57-32/h5-9,13-15,17,26-28,35-41,56H,3-4,10-12,16,18-25H2,1-2H3,(H,53,57)(H,54,66)(H,58,65)(H,59,69)(H,60,70)(H,61,71)(H,62,68)(H,63,72)(H,64,67)(H,73,74)(H4,51,52,55)/t35-,36-,37-,38+,39-,40-,41-/m0/s1

3S,6S,9R,12S,15S,23S)-15-[[(2S)-2-acetamidohexanoyl]amino]-9-benzyl-6-[3-(diaminomethylideneamino)propyl]-12-(1H-imidazol-5-ylmethyl)-3-(1H-indol-3-ylmethyl)-2,5,8,11,14,17-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-23-carboxylic acid

PT-141; PT141; 189691-06-3; Bremelanotida; 6Y24O4F92S; PT-141 FREE BASE; Bremelanotide; PT 141

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)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

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注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

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注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

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口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

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口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

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注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

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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。