314-19-2 Usage
Description
4H-Dibenzo[de,g]quinoline-10,11-diol,5,6,6a,7-tetrahydro-6-methyl-, hydrochloride (1:1), (6aR)-, also known as Apomorphine hydrochloride, is a white or off-white powder or crystal that is soluble in hot water. It is an aporphine alkaloid belonging to the benzoquinoline class. Apomorphine is characterized by its short plasma half-life and significant interpatient variability in its pharmacokinetic profile. It is extensively metabolized through various routes, including sulfation, N-demethylation, glucuronidation, and oxidation.
Uses
Used in Pharmaceutical Industry:
4H-Dibenzo[de,g]quinoline-10,11-diol,5,6,6a,7-tetrahydro-6-methyl-, hydrochloride (1:1), (6aR)is used as an emetic for inducing vomiting in cases of poisoning or drug overdose. It acts as a potent dopamine agonist, stimulating postsynaptic D1and D2-type receptors within the caudate/putamen in the brain.
Used in Parkinson's Disease Treatment:
In the field of neurology, 4H-Dibenzo[de,g]quinoline-10,11-diol,5,6,6a,7-tetrahydro-6-methyl-, hydrochloride (1:1), (6aR)is used as a potential treatment for Parkinson's disease. It is indicated 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. The brand name for this application is Apokyn, developed by Vernalis.
The various routes of administration for Apomorphine hydrochloride include subcutaneous injection, continuous subcutaneous infusion, intravenous infusion, intranasal spray application, sublingual, and rectal administration. It is highly lipophilic, allowing for rapid diffusion across the blood-brain barrier after injection. Dosage adjustments may be necessary in cases of liver and renal impairment.
Originator
Apomorphine
hydrochloride,Nastech
Pharmaceuticals
Company, Inc.
Manufacturing Process
2 Methods of producing of apomorphine
1. The apomorphine was obtained by dehydratation of morphine at heating to
120°C in the presence phosphoric acid and rendering of HCl gas over reaction
mixture.
2. The morphine was converted to β-chloromorphine and then to
dichlorodihydrodesoxymorphine at heating to 140°-150°C in the presence
hydrochloric acid. Then apomorphine is obtained by dehydratation of
dichlorodihydrodesoxymorphine.
Therapeutic Function
Emetic, Expectorant, Hypnotic, Antiparkinsonian,
Dopamine agonist
Biological Activity
Prototypical dopamine agonist (pK i values are 6.43, 7.08, 7.59, 8.36 and 7.83 for human recombinant D 1 , D 2L , D 3 , D 4 and D 5 receptors respectively). Produces biphasic effects on locomotor activity, and displays anti-Parkinsonian and neuroprotective actions following systemic administration in vivo .
Clinical Use
Treatment of refractory motor fluctuations in Parkinson’s
disease
Safety Profile
Poison by intravenous andintraperitoneal routes. Mutation data reported. When heated to decomposition itemits very toxic fumes of NOx and HCl.
Veterinary Drugs and Treatments
Apomorphine is used primarily as an emetic in dogs, and is considered
the emetic of choice for dogs by many clinicians. It is sometimes
used in cats, but its use in this species is somewhat controversial.
Drug interactions
Potentially hazardous interactions with other drugs
Antihypertensives: enhanced hypotensive effect.
Domperidone: possible increased risk of ventricular
arrhythmias.
5HT3
-receptor antagonists: possibly increased
hypotensive effects with ondansetron.
Nitrates: enhanced hypotensive effect.
Metabolism
After subcutaneous injection its fate can be described by
a two-compartment model, with a distribution half-life of
5 (±1.1) minutes and an elimination half-life of 33 (±3.9)
minutes. Clinical response correlates well with levels of
apomorphine in the cerebrospinal fluid.
Apomorphine is extensively metabolised in the liver,
mainly by conjugation with glucuronic acid or sulfate;
the major metabolite is apomorphine sulfate. It is also
demethylated to produce norapomorphine.
Most of a dose is excreted in urine, mainly as metabolites.
Check Digit Verification of cas no
The CAS Registry Mumber 314-19-2 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 3,1 and 4 respectively; the second part has 2 digits, 1 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 314-19:
(5*3)+(4*1)+(3*4)+(2*1)+(1*9)=42
42 % 10 = 2
So 314-19-2 is a valid CAS Registry Number.
InChI:InChI=1/C17H17NO2.ClH/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;1H
314-19-2Relevant articles and documents
PRODUCTION PROCESS OF A HYDROCHLORIC ACID SALT OF APOMORPHINE AND DERIVATIVES THEREOF
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Page/Page column 14; 15; 16, (2021/05/07)
The present invention provides processes for the preparation of a hydrochloric acid salt of compound of formula (2): (I) Compound of formula (2) wherein: R1 is selected from the group consisting of -H, an unsubstiuted straight-chain C1-C20-alkyl, substituted straight-chain C1-C20-alkyl, unsubstituted branched -chain C1-C20-alkyl, substituted branched-chain C1-C20-alkyl, unsubstituted cyclic C3-C20-alkyl, and substituted cyclic C3-C20-alkyl; and R2 is selected from the group consisting of an unsubstituted straight-chain C1-C20-alkyl, substituted straight-chain C1-C20-alkyl, unsubstituted branched-chain C1-C20-alkyl, substituted branched-chain C1-C20-alkyl, unsubstituted cyclic C3-C20-alkyl, substituted cyclic C3-C20-alkyl, unsubstituted -C1-20-alkyl-C3-20-cycloalkyl, substituted -C1-20-alkyl-C3-20-cycloalkyl, unsubstituted allyl and substituted allyl.
FACILE 'ONE POT' PROCESS FOR APOMORPHINE FROM CODEINE
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Page/Page column 5, (2009/04/25)
An improved method for producing apomorphine and derivatives thereof is provided. The method is a convenient 'one-pot' process, comprising the conversion of codeine into apomorphine without isolating the apocodeine intermediate. Use of water reactive scavengers, reagents that will react irreversibly with water, decreases side product formation and allows the use of milder reaction conditions. This one-pot synthesis of apomorphine from codeine provides a faster reaction with improved yields at temperatures lower as compared to conventional methods. The lower operating temperatures and less volatile reactants make the method particularly useful for large-scale manufacturing.
