Quinagolide
Identification
- Name
- Quinagolide
- Accession Number
- DB09097
- Description
Quinagolide is a non-ergot-derived selective dopamine D2 receptor agonist used for the treatment of elevated levels of prolactin or hyperprolactinaemia. Hyperprolalctinaemia is associated with gonadal dysfunction, including infertility and reduced libido, as well as long-term complications such as osteoporosis 1. Newer dopamine receptor agonists such as quinagolide and Cabergoline are shown to effectively inhibit prolactin secretion with improved efficacy over Bromocriptine. These drugs are effective in patients who are intolerant or resistant to Bromocriptine. Quinagolide exists as a racemate and its relevant clinical activity is mediated predominantly by the (-) enantiomer. It is typically present in the hydrochloride salt form and is marketed as oral tablets under the brand name Norprolac contained as a racemate. Quinagolide is currently available in several countries including Canada, but not approved for treatment in the United States.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Quinagolide (DB09097)
- Weight
- Average: 395.56
Monoisotopic: 395.224263109 - Chemical Formula
- C20H33N3O3S
- Synonyms
- (+-)-N,N-Diethyl-N'-((3R*,4aR*,10aS*)-1,2,3,4,4a,5,10,10a-octahydro-6-hydroxy-1-propylbenzo(g)quinolin-3-yl)sulfamide
- Quinagolida
- Quinagolide
- Quinagolidum
Pharmacology
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Indicated for the treatment of hyperprolactinemia (idiopathic or originating from a prolactin-secreting pituitary microadenoma or macroadenoma).
- Associated Conditions
- Contraindications & Blackbox Warnings
Contraindications & Blackbox WarningsWith our commercial data, access important information on dangerous risks, contraindications, and adverse effects.Our Blackbox Warnings cover Risks, Contraindications, and Adverse Effects- Pharmacodynamics
Quinagolide achieves long-lasting reduction in prolactin levels in a dose-proportional effect via selectively targeting D2 receptors as an agonist. It potently suppresses both basal and stimulated serum prolactin levels by exerting a strong inhibitory effect on the secretion of the anterior pituitary hormone prolactin.
- Mechanism of action
Prolactin secretion from the lactotroph cells present in the anterior pituiatry gland is under tonic inhibitory control mediated by dopaminergic signalling via D2 receptors 5. Quinagolide selectively binds to D2 receptors expressed on the surface of lactotroph cells with high affinity which results in reduced adenylyl cyclase activity, reduced intracellular cyclic adenosine monophosphate and inhibited prolactin secretion. It also binds to D1 receptors but with low affinity and little clinical relevance 1.
Target Actions Organism UDopamine D2 receptor agonistHumans UD(1) dopamine receptor agonistHumans - Absorption
The absorption of quinagolide is rapid and extensive with 95% of the dose absorbed after oral ingestion, however the absolute bioavailability is low (4 %) due to pre-systemic metabolism. The time to reach peak plasma concentration is 30-60 minutes. Prolactin-lowering effect of quinagolide at recommended therapeutic doses occurs within 2 hours after ingestion reaches a maximum within 4 to 6 hours and is maintained for at least 24 hours 7.
- Volume of distribution
Approximate volume of distribution is 100L following a single oral admininstration. The parent drug and metabolites is predicted to be extensively distributed in the extravascular compartment with primary target organs being the liver, kidneys, salivary glands and pituitary Label.
- Protein binding
Plasma protein binding is reported to be non-specific with an approximate ratio of 90%.
- Metabolism
Quinagolide undergoes extensive first pass metabolism with sulfate and glucuronide conjugates being the major circulating metabolites. N-desethyl analogue is a biologically active metabolite while sulfate or glucuronide conjugates and N,N-didesethyl analogue are inactive metabolites.
- Route of elimination
More than 95% of total dose is excreted as metabolites and the excretion via urine and feces is approximately equal. Renal elimination accounts for 50% of total elimination, where sulfate or glucuronide conjugates, N-desethyl and N,N-didesethyl analogues can be detected in the urine. Unconjugated forms of sulfate or glucuronide conjugates, N-desethyl and N,N-didesethyl analogues are excreted into feces, and fecal elimination accounts for 40% of the total elimination of the drug.
- Half-life
The terminal half-life for parent drug is 11.5 hours following single dose and 17 hours at steady state.
- Clearance
- Not Available
- Adverse Effects
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Most commonly observed adverse effects are nausea, vomiting, headache, dizziness and fatigue that usually appear in the beginning of initial therapy. Less frequent side effects (1 to 10%) include anorexia, abdominal pain, constipation or diarrhoea, insomnia, oedema, flushing, nasal congestion and hypotension. Orthostatic hypotension may result in faintness or syncope Label. Quinagolide demonstrates carcinogenic potential in animal studies but with no known relevance in humans. It is not demonstrated to be embryotoxic or teratogenic, but it is associated with reduced pregnancy rates 6. Oral LD50 values in mouse, rat and rabbit are 300 mg/kg, 980 mg/kg and 3200 mg/kg, respectively MSDS.
- Affected organisms
- Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAcetophenazine The therapeutic efficacy of Quinagolide can be decreased when used in combination with Acetophenazine. Alimemazine The therapeutic efficacy of Quinagolide can be decreased when used in combination with Alimemazine. Amisulpride The therapeutic efficacy of Quinagolide can be decreased when used in combination with Amisulpride. Amoxapine The therapeutic efficacy of Quinagolide can be decreased when used in combination with Amoxapine. Apomorphine The risk or severity of adverse effects can be decreased when Apomorphine is combined with Quinagolide. Aripiprazole The therapeutic efficacy of Quinagolide can be decreased when used in combination with Aripiprazole. Aripiprazole lauroxil The therapeutic efficacy of Quinagolide can be decreased when used in combination with Aripiprazole lauroxil. Asenapine The therapeutic efficacy of Quinagolide can be decreased when used in combination with Asenapine. Benperidol The therapeutic efficacy of Quinagolide can be decreased when used in combination with Benperidol. Brexpiprazole The therapeutic efficacy of Brexpiprazole can be decreased when used in combination with Quinagolide. 
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- Avoid excessive or chronic alcohol consumption. Alcohol may increase the risk of dizziness, thereby reducing the tolerability of quinagolide.
- Take with a light meal or snack. Food reduces gastric irritation.
Products
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Ingredient UNII CAS InChI Key Quinagolide hydrochloride 33474X943Y 94424-50-7 DVLKVIJLALMCBQ-VENMBWNLSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Norprolac Tablet Oral Ferring Pharmaceuticals 2004-12-29 Not applicable Canada 
Norprolac Tablet Oral Ferring Pharmaceuticals 2004-12-29 Not applicable Canada Norprolac Tablet Oral Ferring Pharmaceuticals 2004-12-29 Not applicable Canada Norprolac Tablet Oral Ferring Pharmaceuticals 2004-12-29 Not applicable Canada
Categories
- ATC Codes
- G02CB04 — Quinagolide
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as benzoquinolines. These are organic compounds containing a benzene fused to a quinoline ring system.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Quinolines and derivatives
- Sub Class
- Benzoquinolines
- Direct Parent
- Benzoquinolines
- Alternative Parents
- Tetralins / Aralkylamines / 1-hydroxy-4-unsubstituted benzenoids / 1-hydroxy-2-unsubstituted benzenoids / Sulfuric acid diamides / Piperidines / Trialkylamines / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds show 2 more
- Substituents
- 1-hydroxy-2-unsubstituted benzenoid / 1-hydroxy-4-unsubstituted benzenoid / Amine / Aralkylamine / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Benzoquinoline / Hydrocarbon derivative / Organic nitrogen compound show 11 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
Chemical Identifiers
- UNII
- 80Q9QWN15M
- CAS number
- 87056-78-8
- InChI Key
- GDFGTRDCCWFXTG-ZIFCJYIRSA-N
- InChI
- InChI=1S/C20H33N3O3S/c1-4-10-22-14-17(21-27(25,26)23(5-2)6-3)11-16-12-18-15(13-19(16)22)8-7-9-20(18)24/h7-9,16-17,19,21,24H,4-6,10-14H2,1-3H3/t16-,17+,19-/m1/s1
- IUPAC Name
- (3S,4aS,10aR)-3-[(diethylsulfamoyl)amino]-1-propyl-1H,2H,3H,4H,4aH,5H,10H,10aH-benzo[g]quinolin-6-ol
- SMILES
- [H][C@]12C[C@@H](CN(CCC)[C@]1([H])CC1=CC=CC(O)=C1C2)NS(=O)(=O)N(CC)CC
References
- General References
- Barlier A, Jaquet P: Quinagolide--a valuable treatment option for hyperprolactinaemia. Eur J Endocrinol. 2006 Feb;154(2):187-95. [PubMed:16452531]
- Di Sarno A, Landi ML, Marzullo P, Di Somma C, Pivonello R, Cerbone G, Lombardi G, Colao A: The effect of quinagolide and cabergoline, two selective dopamine receptor type 2 agonists, in the treatment of prolactinomas. Clin Endocrinol (Oxf). 2000 Jul;53(1):53-60. [PubMed:10931080]
- Schultz PN, Ginsberg L, McCutcheon IE, Samaan N, Leavens M, Gagel RF: Quinagolide in the management of prolactinoma. Pituitary. 2000 Dec;3(4):239-49. [PubMed:11788012]
- Busso C, Fernandez-Sanchez M, Garcia-Velasco JA, Landeras J, Ballesteros A, Munoz E, Gonzalez S, Simon C, Arce JC, Pellicer A: The non-ergot derived dopamine agonist quinagolide in prevention of early ovarian hyperstimulation syndrome in IVF patients: a randomized, double-blind, placebo-controlled trial. Hum Reprod. 2010 Apr;25(4):995-1004. doi: 10.1093/humrep/deq005. Epub 2010 Feb 6. [PubMed:20139430]
- 32. (2012). In Rang and Dale's Pharmacology (7th ed., pp. 397-398). Edinburgh: Elsevier/Churchill Livingstone. [ISBN:978-0-7020-3471-8]
- DRUG NAME: Quinagolide - BC Cancer Agency [Link]
- NORPROLAC® (quinagolide) Product information [Link]
- External Links
- PubChem Compound
- 3086401
- PubChem Substance
- 310265024
- ChemSpider
- 2343034
- BindingDB
- 50225362
- 76887
- ChEBI
- 135627
- ChEMBL
- CHEMBL290962
- ZINC
- ZINC000003778441
- Wikipedia
- Quinagolide
- AHFS Codes
- 92:00.00 — Miscellaneous Therapeutic Agents
- FDA label
- Download (301 KB)
- MSDS
- Download (78.9 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 2 Completed Prevention Ovarian Hyperstimulation Syndrome 1 2 Completed Treatment Ovarian Hyperstimulation Syndrome 1 2 Recruiting Treatment Endometriosis 1 2 Recruiting Treatment Endometriosis related pain / Endometriosis-related Pain 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral Tablet Oral 150 MCG Tablet Oral 25 MCG Tablet Oral 0.025 mg Tablet Oral 0.075 mg Tablet Oral 25 mcg/50mcg Tablet Oral 75 mcg Tablet Oral 25 cg - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 231-237 FDA Label/Product monograph water solubility Sparingly soluble in water (0.2%) FDA Label/Product monograph - Predicted Properties
Property Value Source Water Solubility 0.154 mg/mL ALOGPS logP 2.56 ALOGPS logP 2.5 ChemAxon logS -3.4 ALOGPS pKa (Strongest Acidic) 10.2 ChemAxon pKa (Strongest Basic) 8.22 ChemAxon Physiological Charge 1 ChemAxon Hydrogen Acceptor Count 5 ChemAxon Hydrogen Donor Count 2 ChemAxon Polar Surface Area 72.88 Å2 ChemAxon Rotatable Bond Count 5 ChemAxon Refractivity 109.66 m3·mol-1 ChemAxon Polarizability 44.11 Å3 ChemAxon Number of Rings 3 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter Yes ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Agonist
- General Function
- Potassium channel regulator activity
- Specific Function
- Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
- Gene Name
- DRD2
- Uniprot ID
- P14416
- Uniprot Name
- D(2) dopamine receptor
- Molecular Weight
- 50618.91 Da
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Agonist
- General Function
- G-protein coupled amine receptor activity
- Specific Function
- Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.
Components:
References
- Barlier A, Jaquet P: Quinagolide--a valuable treatment option for hyperprolactinaemia. Eur J Endocrinol. 2006 Feb;154(2):187-95. [PubMed:16452531]
Drug created on September 16, 2015 18:24 / Updated on March 01, 2021 12:05