Absorption, Distribution and Excretion
Apomorphine has a plasma Tmax of 10-20 minutes and a cerebrospinal fluid Tmax. The Cmax and AUC of apomorphine vary significantly between patients, with 5- to 10-fold differences being reported.
Data regarding apomorphine's route of elimination is not readily available. A study in rats has shown apomorphine is predominantly eliminated in the urine.
The apparent volume of distribution of subcutaneous apomorphine is 123-404L with an average of 218L. The apparent volume of distribution of sublingual apomorphine is 3630L.
The clearance of a 15mg sublingual dose of apomorphine is 1440L/h, while the clearance of an intravenous dose is 223L/h.
The plasma-to-whole blood apomorphine concentration ratio is equal to one. Mean (range) apparent volume of distribution was 218 L (123 - 404 L). Maximum concentrations in cerebrospinal fluid (CSF) are less than 10% of maximum plasma concentrations and occur 10 to 20 minutes later.
Apomorphine hydrochloride is a lipophilic compound that is rapidly absorbed (time to peak concentration ranges from 10 to 60 minutes) following subcutaneous administration into the abdominal wall. After subcutaneous administration, apomorphine appears to have bioavailability equal to that of an intravenous administration. Apomorphine exhibits linear pharmacokinetics over a dose range of 2 to 8 mg following a single subcutaneous injection of apomorphine into the abdominal wall in patients with idiopathic Parkinson's disease. /Apomorphine hydrochloride/
In the treatment of patients with Parkinson's disease, apomorphine has an established place as a back-up therapy if other antiparkinsonian drugs, such as levodopa and oral dopamine agonists, have not controlled the existing response fluctuations. Apomorphine is a synthetic derivative of morphine, with a totally distinct pharmacological profile. It is a very lipophilic compound which is easily (auto)oxidized. This (auto)oxidation is the main metabolic route besides glucuronidation and sulfation, which are both responsible for about 10% of the metabolic transformation. Apomorphine quickly passes the nasal and intestinal mucosa as well as the blood-brain barrier (depending on the administration route). Many routes of administration have been explored, but subcutaneous, sublingual, nasal and rectal administration are used in clinical practice. The volume of distribution varies between 1 and 2 times bodyweight. The elimination half-life is very short (30 to 90 min) depending on the type of parenteral administration. Apomorphine is a high clearance drug (3 to 5 L/kg/hr) and is mainly excreted and metabolised by the liver. Only 3 to 4% is excreted unchanged in the urine. The clinical effect of apomorphine can be linked directly to its concentration in the cerebrospinal fluid. Consequently, a 2-compartment model can be used to predict the clinical effects of apomorphine. The pharmacokinetic-pharmacodynamic data reflect the clinical observations of steep dose-effect curves if apomorphine is used in patients with random 'on-off' fluctuations. These dose-effect curves are less steep in stable or 'wearing-off' (end-of-dose deterioration) patients. Intravenous infusions of apomorphine in combination with timed motor assessments can be used clinically to characterize the therapeutic window of a particular patient if dyskinesia persists after single injections of apomorphine. If more population data become available, the population pharmacokinetics-pharmacodynamics of apomorphine could be helpful in predicting the clinical effects of apomorphine in the several subgroups of patients with Parkinson's disease.

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Metabolism / Metabolites
Apomorphine is N-demethylated by CYP2B6, 2C8, 3A4, and 3A5. It can be glucuronidated by various UGTs, or sulfated by SULTs 1A1, 1A2, 1A3, 1E1, and 1B1. Approximately 60% of sublingual apomorphine is eliminated as a sulfate conjugate, though the structure of these sulfate conjugates are not readily available. The remainder of an apomorphine dose is eliminated as apomorphine glucuronide and norapomorphine glucuronide. Only 0.3% of subcutaneous apomorphine is recovered as the unchanged parent drug.
Routes of apomorphine metabolism in humans are not known. Potential metabolic routes include sulfation, N-demethylation, glucuronidation, and oxidation.1 Apomorphine undergoes rapid auto-oxidation in vitro. Cytochrome P-450 (CYP) enzymes play a minor role in the metabolism of apomorphine. In vitro studies have suggested that apomorphine may be metabolized by COMT. Data from in vivo studies indicate that apomorphine is not metabolized by COMT.
Hepatic
Half Life: 40 minutes (range 30 - 60 minutes)

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Biological Half-Life
The terminal elimination half life of a 15mg sublingual dose of apomorphine is 1.7h, while the terminal elimination half life of an intravenous dose is 50 minutes.
The mean terminal elimination half-life is about 40 minutes (range about 30 to 60 minutes).

Hepatotoxicity
Apomorphine has not been reported to cause serum aminotransferase elevations or clinically apparent acute liver injury, but its use has been limited and is typically given in low doses for a limited period of time. Thus, if apomorphine causes liver injury it must be rare.
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 apomorphine during breastfeeding. If apomorphine is required by the mother, it is not a reason to discontinue breastfeeding. However, apomorphine inhibits prolactin release in animals and might interfere with establishment of lactation. An alternate drug may be preferred, especially while nursing a newborn or preterm infant.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Protein Binding
Apomorphine is expected to be 99.9% bound to human serum albumin, as no unbound apomorphine is detected.

[1]. Subcutaneous apomorphine in the treatment of Parkinson's disease. J Neurol Neurosurg Psychiatry. 1990 Feb;53(2):96-101.

[2]. Apomorphine for Parkinson's Disease: Efficacy and Safety of Current and New Formulations. CNS Drugs. 2019 Sep;33(9):905-918.

Apomorphine is an aporphine alkaloid. It has a role as an alpha-adrenergic drug, a serotonergic drug, an antidyskinesia agent, a dopamine agonist, an antiparkinson drug and an emetic. It derives from a hydride of an aporphine.
Apomorphine is a non-ergoline dopamine D2 agonist indicated to treat hypomobility associated with Parkinson's. It was first synthesized in 1845 and first used in Parkinson's disease in 1884. Apomorphine has also been investigated as an emetic, a sedative, a treatment for alcoholism, and a treatment of other movement disorders. Apomorphine was granted FDA approval on 20 April 2004.
Apomorphine is a Dopaminergic Agonist. The mechanism of action of apomorphine is as a Dopamine Agonist.
Apomorphine is a subcutaneously administered dopamine receptor agonist used predominantly in the therapy of hypomobility of advanced Parkinson disease. The use of apomorphine has been limited, but it has not been associated with serum enzyme elevations during treatment nor has it been implicated in cases of acute liver injury.
Apomorphine Hydrochloride is the hydrochloride salt form of apomorphine, a derivative of morphine and non-ergoline dopamine agonist with high selectivity for dopamine D2, D3, D4 and D5 receptors. Apomorphine hydrochloride acts by stimulating dopamine receptors in the nigrostriatal system, hypothalamus, limbic system, pituitary gland, and blood vessels. This enhances motor function, suppresses prolactin release, and causes vasodilation and behavioral effects. Apomorphine hydrochloride is used in the treatment of Parkinson's disease and erectile dysfunction. In addition, apomorphine hydrochloride acts on the chemoreceptor trigger zone and is used as a central emetic in the treatment of drug overdose.
A derivative of morphine that is a dopamine D2 agonist. It is a powerful emetic and has been used for that effect in acute poisoning. It has also been used in the diagnosis and treatment of parkinsonism, but its adverse effects limit its use. [PubChem]
A derivative of morphine that is a dopamine D2 agonist. It is a powerful emetic and has been used for that effect in acute poisoning. It has also been used in the diagnosis and treatment of parkinsonism, but its adverse effects limit its use.
See also: Apomorphine Hydrochloride (has salt form); Apomorphine Diacetate (has salt form).

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Drug Indication
Apomorphine is indicated to treat acute, intermittent treatment of hypomobility, off episodes associated with advanced Parkinson's disease.
FDA Label
Treatment of men with erectile dysfunction, which is the inability to achieve or maintain a penile erection sufficient for satisfactory sexual performance. In order for Uprima to be effective, sexual stimulation is required.
Treatment of men with erectile dysfunction, which is the inability to achieve or maintain a penile erection sufficient for satisfactory sexual performance. In order for Taluvian to be effective, sexual stimulation is required.
Treatment of men with erectile dysfunction, which is the inability to achieve or maintain a penile erection sufficient for satisfactory sexual performance. In order for Ixense to be effective, sexual stimulation is required.

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Mechanism of Action
Apomorphine is a non-ergoline dopamine agonist with high binding affinity to dopamine D2, D3, and D5 receptors. Stimulation of D2 receptors in the caudate-putamen, a region of the brain responsible for locomotor control, may be responsible for apomorphine's action. However, the means by which the cellular effects of apomorphine treat hypomobility of Parkinson's remain unknown.
The exact mechanism of action of apomorphine hydrochloride in the treatment of Parkinson's disease has not been fully elucidated but may involve stimulation of postsynaptic dopamine D2 receptors within the caudate-putamen in the brain. Apomorphine has been shown to improve motor function in an animal model of Parkinson's disease. In particular, apomorphine attenuates the motor deficits associated with neurotoxin (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine ([MPTP])-induced lesions in the ascending nigrostriatal dopaminergic pathway in primates.
Apomorphine hydrochloride is a nonergot-derivative dopamine receptor agonist that is structurally and pharmacologically related to dopamine. In in vitro studies, apomorphine hydrochloride demonstrated a higher affinity for the dopamine D4 receptor than for dopamine D2, D3, or D5 receptors. Apomorphine hydrochloride binds with moderate affinity to alpha-adrenergic (alpha1D, alpha2B, alpha2C) receptors but has little or no affinity for dopamine D1 receptors, serotonergic (5-HT1A, 5-HT2A, 5-HT2B, 5-HT2C) receptors, beta1- or beta2-adrenergic receptors, or histamine H1 receptors. /Apomorphine hydrochloride/

C17H18NO2+

268.33032

267.126

58-00-4

58-00-4;314-19-2 (HCl);41372-20-7 (HCl hydrate);41035-30-7 (S-isomer HCl); 39478-62-1 (S-isomer);

6005

Green to dark green solid powder

1.299 g/cm3

473.4ºC at 760 mmHg

195ºC (decomposes)

268.8ºC

2.787

43.7

2

3

0

20

374

1

CN1CCC2=C3[C@H]1CC4=C(C3=CC=C2)C(=C(C=C4)O)O

VMWNQDUVQKEIOC-CYBMUJFWSA-N

InChI=1S/C17H17NO2/c1-18-8-7-10-3-2-4-12-15(10)13(18)9-11-5-6-14(19)17(20)16(11)12/h2-6,13,19-20H,7-9H2,1H3/t13-/m1/s1

(6aR)-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline-10,11-diol

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。