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Apomorphin
Apomorphin · apomorphine · Apormorphine · ApoMorphine-d3 · Apomorphine 13C D3 · 6aβ-Aporphine-10,11-diol · (6aR)-5,6,6a,7-Tetrahydro-6-methyl-4H-dibenzo[de,g]quinoline-10,11-diol · (6aS)-5,6,6aα,7-Tetrahydro-6-methyl-4H-dibenzo[de,g]quinoline-10,11-diol
Identifikatoren & physikalische Daten
| CAS No. | 41372-20-7 |
|---|---|
| Summenformel | C17H17NO2 |
| Durchschnittliche Molmasse | 267,32 g/mol |
| Monoisotopische Masse | 267,12592878 g/mol |
| SMILES | CN1CCc2cccc3c2[C@H]1Cc1ccc(O)c(O)c1-3 |
| InChIKey | VMWNQDUVQKEIOC-CYBMUJFWSA-N |
| PubChem CID | 6005 |
| ChEMBL | CHEMBL53 |
| ChEBI | CHEBI:48538 |
| EC No. | 200-360-0 |
| DTXSID | DTXSID8022614 |
| Lokaler Name | Apomorphin |
Chemische & physikalische Eigenschaften
| XLogP | 2,3 |
|---|---|
| Polarare Oberfläche (TPSA) | 43,7 |
| H-Brücken-Donoren | 2 |
| H-Brücken-Akzeptoren | 3 |
| Frei drehbare Bindungen | 0 |
| Schwere Atome | 20 |
| Formalladung | 0 |
| Komplexität | 374 |
| Arzneimittel | DEA NFLIS-Drug Category -> NarcoticsPharmaceuticals -> Listed in ZINC15 |
| LogP (Verteilungskoeffizient) | log Kow = 2.303.1 |
| Color/Form | Hexagonal plates from chloroform+petroleum etherrods from ether |
| Löslichkeit | MINUTE, WHITE OR GRAYISH WHITE, GLISTENING CRYSTALS OR WHITE POWDERODORLESSSOLN ARE NEUTRAL TO LITMUSLEVOROTATORY IN DIL ACID1 G SOL IN 50 ML WATER, IN ABOUT 50 ML ALCOHOL, & IN ABOUT 20 ML WATER @ 80 °CPPT BY TANNIC ACID & OTHER ALKALOIDAL PRECIPITANTS & DECOMP BY OXIDIZING AGENTS. /HCL/Sol in alcohol, acetone, chloroformslightly sol in water, benzene, ether, petroleum etherSlightly soluble in hydrochloric acid, ligandsoluble in ethanol, ethyl ether, acetone, benzene, chloroform, alkaliesIn water, 1.66X10+4 mg/L at 16 °C5.10e-01 g/LAqueous Base (Slightly), DMSO (Slightly)20g/L(25 ºC) |
| Human Drugs | BreastfeedingLactationMilk, HumanAntiparkinson AgentsDopamine AgentsDopamine AgonistsEmeticsGastrointestinal AgentsPharmaceuticals |
| Animal Drugs | Pharmaceuticals -> UK Veterinary Medicines Directorate List |
| Decomposition | When heated to decomposition it emits highly toxic fumes of nitroxides. |
| Schmelzpunkt | 195 °C (decomposes)MP: 127-128 °Cspecific optical rotation: -88 deg at 24 °C/D (c = 1.12 in 0.1 N HCl) /Diacetate ester/195°C (rough estimate) |
| Optical Rotation | Small crystals (usually hemihydrate). Decomposes and turn green on exposure to light and air. Specific optical rotation -48 deg at 25 °C/D ( c = 1.2). pH of aqueous solution (1 in 300) = 4.8One gram dissolves in 50 mL water, 17 mL water at 80 °C, 50 mL alcohol. Very slightly soluble in chloroform and ether. /Hydrochloride/ |
| Physical Description | Solid |
| Stability/Shelf Life | The drug is unstable in solution and must be prepared just prior to use ... |
| Dissociation Constants | pKb: 7.0pKa: 8.92 |
| Siedepunkt | 410.51°C (rough estimate) |
| Dichte | 1.0690 (rough estimate) |
| Brechungsindex | 1.5400 (estimate) |
| pKa (Säurekonstante) | 7.0, 8.92(at 25℃) |
| Aggregatzustand | Solid |
| Farbe | White, crystalline alkaloid |
| Stabilität | Hygroscopic |
Sicherheit & Vorschriften
| FDA-Anforderungen | The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl apomorphine hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Apomorphine hydrochloride/ |
|---|---|
| Entsorgungsverfahren | SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices. |
| Wechselwirkungen | Based on reports of profound hypotension and loss of consciousness when apomorphine was administered with ondansetron, the concomitant use of apomorphine with drugs of the 5HT3 antagonist class (including, for example, ondansetron, granisetron , dolasetron, palonosetron, and alosetron) is contraindicated.Potential pharmacologic interaction (additive sedative and hypotensive effects) with alcohol. Potential pharmacologic interaction with CNS depressants (additive sedative effects).Hypotensive Agents and Vasodilators: Potential pharmacologic interaction (additive hypotensive effects)use with caution. Hypotension, myocardial infarction, pneumonia, serious falls, and bone and joint injuries reported more frequently in patients receiving concomitant antihypertensive drugs or vasodilators. The mechanism underlying many of these events is unknown, but may be associated with hypotension.Potential pharmacologic interaction (reduced efficacy of apomorphine) when apomorphine is used with certain antipsychotic agents (e.g., phenothiazines, butyrophenones, thioxanthenes) or metoclopramide. Patients with major psychosis receiving certain antipsychotic agents (e.g., phenothiazines, butyrophenones, thioxanthenes) should receive dopamine agonists only if benefit outweighs risk.For more Interactions (Complete) data for APOMORPHINE (6 total), please visit the HSDB record page. |
| 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. |
| Expositionspfade | 100% following subcutaneous administration |
| Toxizitätsübersicht | 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. |
| Human Toxicity Excerpts | /SIGNS AND SYMPTOMS/ This study was undertaken to ascertain the histopathology and etiology of cutaneous nodules observed in Parkinson's patients treated with continuous subcutaneous apomorphine. Ten patients were recruited, answered questionnaires, and underwent skin biopsies and full blood count, and nine were patch tested to apomorphine and its preservative. Six had serum IgE levels measured. A florid panniculitis was seen in all biopsiesfive were predominantly eosinophilic, three lymphocytic and two neutrophilicin seven cases the panniculitis was mixed and in three it was septal. Patch testing was universally negative and the IgE levels were normal./SIGNS AND SYMPTOMS/ A rarely reported motivation for apomorphine abuse (escalation of dose beyond prescribed frequency) is the use of apomorphine to attempt to avoid all symptoms of all "off" events when "off" events occur frequently. A second, rarely reported, motivation for apomorphine abuse is a psychosexual reaction related to the stimulation of penile erection and increase in libido. Adverse events that have been reported in males with overuse include frequent penile erections, atypical sexual behavior, heightened libido, dyskinesias, agitation, confusion, and depression. No studies have been conducted to evaluate the potential for dependence when apomorphine is used as acute (rescue) treatment of "off" episodes in the patients with "on/off" or "wearing-off" effects associated with late stage Parkinson's disease./SIGNS AND SYMPTOMS/ Increased incidence of confusion, hallucinations, serious adverse events (life-threatening events or events resulting in hospitalization and/or increased disability), falls, cardiovascular events, respiratory disorders, and GI events in geriatric individuals relative to younger adults./CASE REPORTS/ A similar pattern of psychosexual disorders has been observed after long-term treatment with levodopa therapy in four male parkinsonian patients treated with apomorphine for severe on-off motor fluctuations. An acute episode in each case had led them to the hospital in the context of a psychiatric emergency (after punishable sexual acts in two cases). In each case, this episode had been preceded by an increase of self-administered apomorphine, whereas other antiparkinsonian drugs remained unchanged. Questioning had revealed psychosexual disturbances as early as the onset of apomorphine treatment, which tended to progressively worsen with the number of apomorphine daily doses. A decrease in the dosage of apomorphine had been followed by the improvement of the psychiatric condition without worsening of the motor status. Recurrence of psychiatric disorders with similar features had been observed when two patients again increased the number of apomorphine daily injections. The absence of somatic manifestations when apomorphine treatment was withdrawn or reduced, with persistence of psychosexual disturbances, could suggest a psychological dependence from the drug.For more Human Toxicity Excerpts (Complete) data for APOMORPHINE (7 total), please visit the HSDB record page. |
| Carcinogen Classification | No indication of carcinogenicity to humans (not listed by IARC). |
| Drug Induced Liver Injury | Drug-Induced Liver Injury Severity and Toxicity (DILIst)apomorphineDILI NegativeSubcutaneousDOI:10.1016/j.drudis.2019.09.022 |
| Non-Human Toxicity Excerpts | /LABORATORY ANIMALS: Neurotoxicity/ It has been proposed that apomorphine and other dopamine receptor agonists might induce neurotoxicity mediated by their quinone and semiquinone oxidation derivatives. The aim of the present study was to evaluate the possible neurobehavioral effects of apomorphine and its oxidation derivative, 8-oxo-apomorphine-semiquinone (8-OASQ). Adult female Wistar rats were treated with a systemic injection of apomorphine (0.05 or 0.5 mg/kg) or 8-OASQ (0.05 or 0.5 mg/kg) 20 min before behavioral testing. Apomorphine and 8-OASQ induced differential impairing effects on short- and long-term retention of an inhibitory avoidance task. Apomorphine, but not 8-OASQ, dose-dependently impaired habituation to a novel environment. The memory-impairing effects could not be attributed to reduced nociception or other nonspecific behavioral alterations, since neither apomorphine nor 8-OASQ affected footshock reactivity or behavior during exploration of an open field. The results suggest that oxidation products of dopamine or dopamine receptor agonists might induce cognitive deficits./GENOTOXICITY/ Apomorphine was mutagenic in the in vitro bacterial Ames test and the in vitro mammalian mouse lymphoma assay. Apomorphine was also clastogenic ... in the in vitro mouse lymphoma assay. Apomorphine was negative in the in vivo micronucleus assay in mice./GENOTOXICITY/ /It was/ investigated whether systemic injection of apomorphine and its oxidation derivative 8-oxo-apomorphine-semiquinone (8-OASQ) could induce DNA damage in mice brain, using the single-cell gel assay. 8-OASQ induced DNA damage in the brains at 1 and 3 hr, but not at 24 hr after treatment whereas apomorphine induced a slight increase in brain DNA damage frequency at 3 hr after treatment, suggesting that both drugs display genotoxic activity in brain tissue./ALTERNATIVE and IN VITRO TESTS/ ... Apomorphine cytotoxicity /was investigated/ by incubating cultures of rat glioma C6 cells and primary cultures of neurons with different concentrations of the drug. Apomorphine-promoted cell death was proportional to its concentration and was time-dependent. The ED(50) of apomorphine on C6 cell death after 48 hr was about 200 uM. The cytotoxic effects induced by apomorphine were correlated to its autoxidation, which leads to the formation of reactive oxygen species, semiquinones, quinones, and a melanin-like pigment. C6 cells that underwent treatment with 400 uM apomorphine for 6 hr displayed features of necrosis, including loss of membrane integrity, degeneration of mitochondria, and DNA fragmentation. Thiols, such as cysteine, N-acetyl-L-cysteine, and glutathione, significantly protected cultured neurons and C6 cells against apomorphine-induced cytotoxicity. Thiols also inhibited apomorphine autoxidation. These data strongly suggest that apomorphine cytotoxicity towards neurons and C6 cells results from an intracellular oxidative stress.For more Non-Human Toxicity Excerpts (Complete) data for APOMORPHINE (8 total), please visit the HSDB record page. |
| Populations at Special Risk | The commercially available formulation of apomorphine hydrochloride injection contains sodium metabisulfite, which can cause serious allergic-type reactions in certain susceptible individuals. The overall prevalence of sulfite sensitivity in the general population is probably low, but in susceptible individuals, exposure to sulfites can result in acute bronchospasm or, less frequently, life-threatening anaphylaxis. Sulfite sensitivity appears to occur more frequently in asthmatic than in nonasthmatic individuals. |
| Antidote and Emergency Treatment | Emergency and supportive measures: Maintain an open airway and assist ventilation if necessary. Administer supplemental oxygen. Treat coma, seizures, hypotension, and noncardiogenic pulmonary edema if they occur. /Opiates and opioids/Specific drugs and antidotes: Naloxone is a specific opioid antagonist with no agonist properties of its ownlarge doses may be given safely. ... Caution: The duration of the effect of naloxone (1-2 hours) is shorter than that of many opioids. Therefore, do not release a patient who has awakened after naloxone treatment until at least 3-4 hours has passed since the last dose of naloxone. In general, if naloxone was required to reverse opioid-induced coma, it is safer to admit the patient for at least 6-12 hours of observation. Nalmefene is an opioid antagonist with a longer duration of effect (3-5 hours). ... /Opiates and opioids/Decontamination. Administer activated charcoal orally if conditions are appropriate. Gastric lavage is not necessary after small to moderate ingestions if activated charcoal can be given promptly. ... /Opiates and opioids/Enhanced elimination. Because of the very large volumes of distribution of the opioids and the availability of an effective antidotal treatment, there is no role for enhanced elimination procedures. /Opiates and opioids/For more Antidote and Emergency Treatment (Complete) data for APOMORPHINE (7 total), please visit the HSDB record page. |
| Effects During Pregnancy and Lactation | ◉ Summary of Use during Lactation |
| Toxicity Data | LD50: 0.6 mmoles/kg (Intraperitoneal, Mouse) (A308) |
| Toxizität | LD50 oral in mouse: > 100mg/kg |
| Gefahrstoffdaten | 58-00-4(Hazardous Substances Data) |
Anwendungen & Verwendung
Verwenden
To treat acute poisoning; in the diagnosis and treatment of parkinsonism; a weak sensitizer and a powerful emetic.