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药品详细

Apomorphine(阿朴吗啡)

化学结构式图
中文名
阿朴吗啡
英文名
Apomorphine
分子式
C17H17NO2
化学名
(9R)-10-methyl-10-azatetracyclo[7.7.1.0^{2,7}.0^{13,17}]heptadeca-1(16),2(7),3,5,13(17),14-hexaene-3,4-diol
分子量
Average: 267.3224
Monoisotopic: 267.125928793
CAS号
41372-20-7
ATC分类
G04B 未知;N04B 未知
药物类型
small molecule
阶段
approved
商品名
Apokyn (Mylan);Ixense (Takeda (discontinued));Uprima (Abbott (discontinued));
同义名
Apomorfin;apomorphine;Apomorphine Hydrochloride;Apomorphine Hydrochloride Hemihydrate;Apomorphinium Chloride Hemihydrate;Apormorphine;L-Apomorphine;VR-040;VR-400;VR004;
基本介绍

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]

生产厂家
  • Ipsen biopharm ltd
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Matsumoto K, Yoshida M, Andersson KE, Hedlund P: Effects in vitro and in vivo by apomorphine in the rat corpus cavernosum. Br J Pharmacol. 2005 Sep;146(2):259-67. Pubmed
  2. SCHWAB RS, AMADOR LV, LETTVIN JY: Apomorphine in Parkinson’s disease. Trans Am Neurol Assoc. 1951;56:251-3. Pubmed
  3. Cotzias GC, Papavasiliou PS, Fehling C, Kaufman B, Mena I: Similarities between neurologic effects of L-dipa and of apomorphine. N Engl J Med. 1970 Jan 1;282(1):31-3. Pubmed
  4. Corsini GU, Del Zompo M, Gessa GL, Mangoni A: Therapeutic efficacy of apomorphine combined with an extracerebral inhibitor of dopamine receptors in Parkinson’s disease. Lancet. 1979 May 5;1(8123):954-6. Pubmed
  5. Chaudhuri KR, Clough C: Subcutaneous apomorphine in Parkinson’s disease. BMJ. 1998 Feb 28;316(7132):641. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes
  • Benzylisoquinolines
  • Alkaloids and Alkaloid Derivatives
Substructures
  • Hydroxy Compounds
  • Phenols and Derivatives
  • Naphthalenes
  • Phenylpropenes
  • Benzylisoquinolines
  • Benzene and Derivatives
  • Biphenyl and Derivatives
  • Alkaloids and Alkaloid Derivatives
  • Aliphatic and Aryl Amines
  • Phenanthrenes
  • Catechols
  • Phenethylamines
  • Heterocyclic compounds
  • Aromatic compounds
  • (Iso)quinolines and Derivatives
  • Phenyl Esters
  • Amphetamines
  • Catecholamines and Derivatives
适应症
PARKINSON 帕金森氏症;
药理
Indication For the acute, intermittent treatment of hypomobility, off episodes (end-of-dose wearing off and unpredictable on/off episodes) associated with advanced Parkinson's disease.
Pharmacodynamics Apomorphine is a type of dopaminergic agonist, a morphine derivative which primarily affects the hypothalamic region of the brain. Drugs containing this substance are sometimes used in the treatment of Parkinson's disease or erectile dysfunction. In higher doses it is a highly effective emetic.
Mechanism of action The precise mechanism of action of apomorphine as a treatment for Parkinson's disease is unknown, although it is believed to be due to stimulation of post-synaptic dopamine D2-type receptors within 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 induced by lesions in the ascending nigrostriatal dopaminergic pathway with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in primates.
Absorption 100% following subcutaneous administration
Volume of distribution
  • 123 to 404 L
Protein binding ~50%-albumin
Metabolism
Hepatic
Route of elimination Not Available
Half life 40 minutes (range 30 - 60 minutes)
Clearance
  • 223 L/hr
Toxicity LD50=0.6 mmoles/kg (mice, intraperitoneal)
Affected organisms
  • Humans and other mammals
Pathways Not Available
理化性质
Properties
State solid
Experimental Properties
Property Value Source
water solubility 1.66E+004 mg/L Not Available
logP 3.1 Not Available
pKa 8.92 Not Available
Predicted Properties
Property Value Source
water solubility 5.10e-01 g/l ALOGPS
logP 2.51 ALOGPS
logP 2.87 ChemAxon
logS -2.7 ALOGPS
pKa (strongest acidic) 6.58 ChemAxon
pKa (strongest basic) 13.25 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 3 ChemAxon
hydrogen donor count 2 ChemAxon
polar surface area 43.7 ChemAxon
rotatable bond count 0 ChemAxon
refractivity 79.99 ChemAxon
polarizability 29.7 ChemAxon
药物相互作用
Drug Interaction
Artemether Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Entacapone Entacapone increases the effect and toxicity of the sympathomimetic, apomorphine.
Lumefantrine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Paliperidone The atypical antipsychotic agent, paliperidone, may decrease the therapeutic effect of the anti-Parkinson's agent, apomorphine. This interaction may be due to the dopamine antagonist properties of paliperidone. Consider an alternate antipsychotic in those with Parkinson's disease or consider using clozapine or quetiapine if an atypical antipsychotic is necessary.
Tacrolimus Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Thiothixene May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Thiothixene may also antagonize the effects of the anti-Parkinsonian agent, Apomorphine. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of both agents if concomitant therapy is initiated, discontinued or doses changed.
Toremifene Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Voriconazole Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Vorinostat Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Ziprasidone Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.
Zuclopenthixol Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP). Antagonism may also occur between zuclopenthixol, a dopamine D2 receptor antagonist, and apomorphine, a dopamine agonist. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of both agents if concurrent therapy is initiated, discontinued or dose(s) changed.
食物相互作用
Not Available

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