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Chemistry

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Also known as: Quinidine sulfate, 50-54-4, Dtxsid80911600, Hms3263i19, Ccg-222313, Lp01009
Molecular Formula
C40H50N4O8S
Molecular Weight
746.9  g/mol
InChI Key
RONWGALEIBILOG-QJEGDNEGSA-N

Quinidine sulphate
An optical isomer of quinine, extracted from the bark of the CHINCHONA tree and similar plant species. This alkaloid dampens the excitability of cardiac and skeletal muscles by blocking sodium and potassium currents across cellular membranes. It prolongs cellular ACTION POTENTIALS, and decreases automaticity. Quinidine also blocks muscarinic and alpha-adrenergic neurotransmission.
1 2D Structure

Quinidine sulphate

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
(S)-[(2R,5R)-5-ethenyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxyquinolin-4-yl)methanol;sulfuric acid
2.1.2 InChI
InChI=1S/2C20H24N2O2.H2O4S/c2*1-3-13-12-22-9-7-14(13)10-19(22)20(23)16-6-8-21-18-5-4-15(24-2)11-17(16)18;1-5(2,3)4/h2*3-6,8,11,13-14,19-20,23H,1,7,9-10,12H2,2H3;(H2,1,2,3,4)/t2*13-,14?,19+,20-;/m00./s1
2.1.3 InChI Key
RONWGALEIBILOG-QJEGDNEGSA-N
2.1.4 Canonical SMILES
COC1=CC2=C(C=CN=C2C=C1)C(C3CC4CCN3CC4C=C)O.COC1=CC2=C(C=CN=C2C=C1)C(C3CC4CCN3CC4C=C)O.OS(=O)(=O)O
2.1.5 Isomeric SMILES
COC1=CC2=C(C=CN=C2C=C1)[C@@H]([C@H]3CC4CCN3C[C@@H]4C=C)O.COC1=CC2=C(C=CN=C2C=C1)[C@@H]([C@H]3CC4CCN3C[C@@H]4C=C)O.OS(=O)(=O)O
2.2 Synonyms
2.2.1 MeSH Synonyms

1. Adaquin

2. Apo Quinidine

3. Apo-quinidine

4. Chinidin

5. Quincardine

6. Quinidex

7. Quinidine

8. Quinidine Sulfate

9. Quinora

10. Sulfate, Quinidine

2.2.2 Depositor-Supplied Synonyms

1. Quinidine Sulfate

2. 50-54-4

3. Dtxsid80911600

4. Hms3263i19

5. Ccg-222313

6. Lp01009

7. Eu-0101009

8. Q0010

9. Q 0875

10. Sulfuric Acid--6'-methoxycinchonan-9-ol (1/2)

11. 11034-22-3

2.3 Create Date
2005-08-08
3 Chemical and Physical Properties
Molecular Weight 746.9 g/mol
Molecular Formula C40H50N4O8S
Hydrogen Bond Donor Count4
Hydrogen Bond Acceptor Count12
Rotatable Bond Count8
Exact Mass746.33493574 g/mol
Monoisotopic Mass746.33493574 g/mol
Topological Polar Surface Area174 Ų
Heavy Atom Count53
Formal Charge0
Complexity538
Isotope Atom Count0
Defined Atom Stereocenter Count6
Undefined Atom Stereocenter Count2
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count3
4 Drug and Medication Information
4.1 Drug Information
1 of 2  
Drug NameQuinidine sulfate
Drug LabelQuinidine is an antimalarial schizonticide and an antiarrhythmic agent with class 1A activity; it is the -isomer of quinine, and its molecular weight is 324.43. dQuinidine sulfate is the sulfate salt of quinidine; its chemical name is cinchonan-9-ol,...
Active IngredientQuinidine sulfate
Dosage FormTablet, extended release; Tablet
RouteOral
Strength200mg; 300mg
Market StatusPrescription
CompanySandoz; Watson Labs; Teva Pharms; Mutual Pharm

2 of 2  
Drug NameQuinidine sulfate
Drug LabelQuinidine is an antimalarial schizonticide and an antiarrhythmic agent with class 1A activity; it is the -isomer of quinine, and its molecular weight is 324.43. dQuinidine sulfate is the sulfate salt of quinidine; its chemical name is cinchonan-9-ol,...
Active IngredientQuinidine sulfate
Dosage FormTablet, extended release; Tablet
RouteOral
Strength200mg; 300mg
Market StatusPrescription
CompanySandoz; Watson Labs; Teva Pharms; Mutual Pharm

4.2 Therapeutic Uses

MEDICATION (VET): OF 6 ANTIARRHYTHMICS TESTED, QUINIDINE BISULFATE GAVE NO PROTECTION AGAINST THE INDUCED ARRHYTHMIA IN DOGS.

FERNANDEZ MZ ET AL; REV COLOMB CIENC QUIM-FARM 3 (3): 65 (1979)


... IS EFFECTIVE FOR SHORT- AND LONG-TERM TREATMENT OF SUPRAVENTRICULAR AND VENTRICULAR ARRHYTHMIAS. /QUINIDINE/

Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 854


FOR PRACTICAL PURPOSES, QUINIDINE IS ONLY GIVEN ORALLY, ALTHOUGH IT CAN BE ADMINEITHER IM OR IV UNDER SPECIAL CIRCUMSTANCES. THE USUAL ORAL DOSE OF QUINIDINE SULFATE IS 200 TO 300 MG THREE TO FOUR TIMES A DAY. ... FOR PATIENTS WITH PREMATURE ATRIAL OR VENTRICULAR CONTRACTIONS OR MAINTENANCE THERAPY. HIGHER AND/OR MORE FREQUENT DOSES CAN BE USED FOR LIMITED PERIODS FOR TREATMENT OF PAROXYSMAL VENTRICULAR TACHYCARDIA.

Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 853


Quinidine is used primarily as prophylactic therapy to maintain normal sinus rhythm after conversion of atrial fibrillation and/or flutter by other methods. The drug is also used to prevent the recurrence of paroxysmal atrial fibrillation, paroxysmal atrial tachycardia, paroxysmal atrioventricular junctional rhythm, paroxysmal ventricular tachycardia, and atrial or ventricular premature contractions.

McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 93. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1993 (Plus Supplements, 1993)., p. 993


For more Therapeutic Uses (Complete) data for QUINIDINE SULFATE (7 total), please visit the HSDB record page.


4.3 Drug Warning

OCCASIONALLY PATIENTS TAKING QUINIDINE EXPERIENCE SYNCOPE OR SUDDEN DEATH. ... MAY BE RESULT OF HIGH CONCENTRATIONS OF QUINIDINE IN PLASMA OR RESULT OF COEXISTING DIGITALIS TOXICITY. /QUINIDINE/

Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 853


INDIVIDUALS WITH THE LONG Q-T SYNDROME OR THOSE WHO RESPOND TO LOW CONCENTRATIONS OF QUINIDINE WITH MARKED LENGTHENING OF THE Q-T INTERVAL APPEAR TO BE PARTICULARLY AT RISK /OF SYNCOPE OR SUDDEN DEATH/ AND SHOULD NOT BE TREATED WITH THIS DRUG. /QUINIDINE/

Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 853


EXCESSIVE CONCENTRATION OF DRUG IN PLASMA WILL CAUSE ADVERSE EFFECTS IN ANY PATIENT. BECAUSE QUINIDINE HAS LOW THERAPEUTIC RATIO, CONSTANT VIGILANCE IS THUS REQUIRED IN EVERY PATIENT TAKING THIS DRUG. /QUINIDINE/

Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 853


Quinidine should be used with extreme caution, if at all, in patients with incomplete atrioventricular nodal block, since complete heart block and asystole may result. Im or iv administration of quinidine is especially hazardous in the presence of atrioventricular block, in the absence of atrial activity, and the patients with extensive myocardial injury. Hypokalemia, hypoxia, and disorders of acid base balance must be eliminated as potentiating factors in patients who require large doses of antiarrhythmic agents to control ventricular arrhythmias.

McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 93. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1993 (Plus Supplements, 1993)., p. 995


For more Drug Warnings (Complete) data for QUINIDINE SULFATE (24 total), please visit the HSDB record page.


5 Pharmacology and Biochemistry
5.1 MeSH Pharmacological Classification

Adrenergic alpha-Antagonists

Drugs that bind to but do not activate alpha-adrenergic receptors thereby blocking the actions of endogenous or exogenous adrenergic agonists. Adrenergic alpha-antagonists are used in the treatment of hypertension, vasospasm, peripheral vascular disease, shock, and pheochromocytoma. (See all compounds classified as Adrenergic alpha-Antagonists.)


Enzyme Inhibitors

Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. (See all compounds classified as Enzyme Inhibitors.)


Anti-Arrhythmia Agents

Agents used for the treatment or prevention of cardiac arrhythmias. They may affect the polarization-repolarization phase of the action potential, its excitability or refractoriness, or impulse conduction or membrane responsiveness within cardiac fibers. Anti-arrhythmia agents are often classed into four main groups according to their mechanism of action: sodium channel blockade, beta-adrenergic blockade, repolarization prolongation, or calcium channel blockade. (See all compounds classified as Anti-Arrhythmia Agents.)


Muscarinic Antagonists

Drugs that bind to but do not activate MUSCARINIC RECEPTORS, thereby blocking the actions of endogenous ACETYLCHOLINE or exogenous agonists. Muscarinic antagonists have widespread effects including actions on the iris and ciliary muscle of the eye, the heart and blood vessels, secretions of the respiratory tract, GI system, and salivary glands, GI motility, urinary bladder tone, and the central nervous system. (See all compounds classified as Muscarinic Antagonists.)


Antimalarials

Agents used in the treatment of malaria. They are usually classified on the basis of their action against plasmodia at different stages in their life cycle in the human. (From AMA, Drug Evaluations Annual, 1992, p1585) (See all compounds classified as Antimalarials.)


Voltage-Gated Sodium Channel Blockers

A class of drugs that inhibit the activation of VOLTAGE-GATED SODIUM CHANNELS. (See all compounds classified as Voltage-Gated Sodium Channel Blockers.)


Cytochrome P-450 CYP2D6 Inhibitors

Drugs and compounds which inhibit or antagonize the biosynthesis or actions of CYTOCHROME P-450 CYP2D6. (See all compounds classified as Cytochrome P-450 CYP2D6 Inhibitors.)


5.2 FDA Pharmacological Classification
5.2.1 Pharmacological Classes
Cytochrome P450 2D6 Inhibitor [EPC]; Cytochrome P450 2D6 Inhibitors [MoA]; Antiarrhythmic [EPC]
5.3 Absorption, Distribution and Excretion

ABOUT 90% OF QUINIDINE IN PLASMA IS BOUND TO PLASMA PROTEINS (ALPHA/ACID GLYCOPROTEIN AND ALBUMIN) THE DRUG ENTERS ERYTHROCYTES & ... BINDS TO HEMOGLOBIN; AT STEADY STATE, CONCN OF QUINIDINE IN PLASMA & ERYTHROCYTES ARE APPROXIMATELY EQUAL. QUINIDINE ACCUMULATES RAPIDLY IN MOST TISSUES EXCEPT BRAIN, & ... VOL OF DISTRIBUTION IS 2-3 L/KG. /QUINIDINE/

Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 852


METABOLITES AND SOME OF THE PARENT DRUG (20%) ARE EXCRETED IN URINE; ELIMINATION HALF-TIME IS ABOUT 6 HR. /QUINIDINE/

Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 852


LIVER METABOLISM & RENAL EXCRETION ARE THE MAIN ROUTES OF ELIMINATION. ENTEROHEPATIC CIRCULATION WOULD NOT SIGNIFICANTLY ALTER ABSORPTION KINETICS AS REFLECTED BY BLOOD CONCENTRATION.

PMID:7264866 KOSKAS J ET AL; J PHARM BELG 36 (3): 193 (1981)


PEAK PLASMA CONCN OF 0.29 UG/ML OF QUINIDINE WERE MEASURED @ 4 HR AFTER ADMIN OF SUSTAINED RELEASE CAPSULE (250 MG QUINIDINE BISULFATE) AND DECLINED STEADILY DURING THE NEXT 8 HR, WHILE AFTER ADMIN OF SUSTAINED RELEASE TABLET (300 MG QUINIDINE SULFATE) THEY WERE FAIRLY EVEN DURING 2-10 HR AFTER DOSING. PLASMA CONCENTRATIONS WERE HIGHER AT LATER TIMES FOR THE CAPSULE THAN FOR THE TABLET. THE BIOAVAILABILITY OF QUINIDINE FROM THE CAPSULES DURING 12 HR WAS 184% COMPARED TO THE TABLET. MEAN QUINIDINE PLASMA CONCN WERE SIGNIFICANTLY GREATER @ 3, 4, 6, 8, & 10 HR AFTER ADMIN OF THE CAPSULE THAN AFTER THE TABLET.

CHASSEAUD LF ET AL; PHARM IND 38 (5): 488 (1976)


For more Absorption, Distribution and Excretion (Complete) data for QUINIDINE SULFATE (24 total), please visit the HSDB record page.


5.4 Metabolism/Metabolites

QUINIDINE YIELDS 2'-HYDROXYQUINIDINE AS METABOLITE IN MAN. /QUINIDINE; FROM TABLE/

Goodwin, B.L. Handbook of Intermediary Metabolism of Aromatic Compounds. New York: Wiley, 1976., p. Q-3


MOST URINARY METABOLITES ARE HYDROXYLATED AT ONLY ONE SITE, EITHER ON THE QUINOLINE RING OR ON THE QUINUCLIDINE RING; SMALL AMOUNTS OF DIHYDROXY COMPOUNDS ARE ALSO FOUND. THE FRACTION OF A DOSE OF QUINIDINE THAT IS METABOLIZED & THE METABOLIC PATHWAY APPEAR TO VARY CONSIDERABLY FROM PATIENT TO PATIENT.

Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 852


Quinidine is metabolized in the liver, principally via hydroxylation to 3-hydroxyquinidine and 2-quinidinone. The metabolites may be pharmacologically active. Approximately 10-50% of a dose is excreted in urine (probably by glomerular filtration) as unchanged drug within 24 hr. /Quinidine/

McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 93. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1993 (Plus Supplements, 1993)., p. 993


5.5 Biological Half-Life

THE ELIMINATION HALF-LIFE OF QUINIDINE RANGES FROM 4 TO 10 HR IN HEALTHY PERSONS, WITH USUAL MEAN VALUE OF 6 TO 7 HR. HALF-LIFE IS SIGNIFICANTLY PROLONGED IN ELDERLY PERSONS, EVEN WHEN THEY ARE APPARENTLY HEALTHY. /QUINIDINE/

Miller, R. R., and D. J. Greenblatt. Handbook of Drug Therapy. New York: Elsevier North Holland, 1979., p. 299


... EXCRETED IN URINE; ELIMINATION HALF-TIME IS ABOUT 6 HR. /QUINIDINE/

Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 852


Quinidine generally has a plasma half-life of 6-8 hr in healthy individuals, but half-life may range from 3-16 hr or longer. In one study in patients with Plasmodium falciparum malaria, the elimination half-life of the drug averaged 12.8 hr (range: 6.6-24.8 hr). /Quinidine/

McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 93. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1993 (Plus Supplements, 1993)., p. 993


5.6 Mechanism of Action

IN EXPERIMENTAL ANIMALS, QUINIDINE HAS VERY SIGNIFICANT ATROPINE LIKE ACTION, BLOCKING EFFECTS OF VAGAL STIMULATION OR OF ACETYLCHOLINE. ... ALSO HAS ALPHA-ADRENERGIC BLOCKING PROPERTIES. THIS CAN CAUSE VASODILATATION &, VIA BARORECEPTORS, ACTIVE SYMPATHETIC EFFERENT ACTIVITY. TOGETHER, CHOLINERGIC BLOCKAGE & INCR BETA-ADRENERGIC ACTIVITY CAUSED BY QUINIDINE CAN INCR SINUS RATE & ENHANCE ATRIOVENTRICULAR NODAL CONDUCTION. /QUINIDINE/

Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 851


CAN CAUSE SEVERE DEPRESSION OF SINUS NODE IN PATIENTS WITH THE SICK SINUS SYNDROME ... QUINIDINE CAN INCR SINUS RATE BY CHOLINERGIC BLOCKADE OR BY REFLEXLY INCR SYMPATHETIC ACTIVITY. ... THERAPEUTIC CONCN OF QUINIDINE ... DECR FIRING RATE OF CARDIAC PURKINJE FIBERS BY DIRECT ACTION ... DECR SLOPE OF PHASE 4 DEPOLARIZATION AND SHIFTS THRESHOLD VOLTAGE TOWARD ZERO. /QUINIDINE/

Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 850


... INCR DIASTOLIC ELECTRICAL CURRENT THRESHOLD IN ATRIAL & VENTRICULAR MUSCLE & IN PURKINJE FIBERS ... ALSO INCR FIBRILLATION THRESHOLD IN ATRIA & VENTRICLES. /QUINIDINE/

Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 850


REENTRANT ARRYTHMIAS ARE ABOLISHED BY /QUINIDINE/. THEIR EFFECT ON EFFECTIVE REFRACTORY PERIOD, RESPONSIVENESS, & CONDUCTION. FOR EXAMPLE, WHEN VENTRICULAR PREMATURE DEPOLARIZATIONS ARE CAUSED BY REENTRY IN LOOPS OF PURKINJE FIBERS, ONE WAY BLOCK CAN BE CONVERTED TO TWO WAY BLOCK, THUS MAKING REENTRY IMPOSSIBLE. /QUINIDINE/

Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 850


For more Mechanism of Action (Complete) data for QUINIDINE SULFATE (9 total), please visit the HSDB record page.


API SUPPLIERS

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Buchler GmbH

Germany

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PT KIMIA FARMA PERSERO TBK

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PT Sinkona

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Buchler GmbH

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Zhuhai Rundu Pharmaceutical

China

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Sibbiotech

Russia

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Inga Pharmaceuticals

India

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Vital Laboratories Private Limited

India

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API Reference Price

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08-Feb-2023
02-Jan-2024
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Drugs in Development

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Details:

Termination of development of the novel compound AVP-786 (deudextromethorphan HBr), in development for the treatment of agitation associated with dementia due to Alzheimer's.


Lead Product(s): Deudextromethorphan Hydrobromide,Quinidine sulphate

Therapeutic Area: Neurology Brand Name: AVP-786

Study Phase: Phase IIIProduct Type: Small molecule

Sponsor: Not Applicable

Deal Size: Not Applicable Upfront Cash: Not Applicable

Deal Type: Not Applicable May 22, 2024

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01

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Details : Termination of development of the novel compound AVP-786 (deudextromethorphan HBr), in development for the treatment of agitation associated with dementia due to Alzheimer's.

Brand Name : AVP-786

Molecule Type : Small molecule

Upfront Cash : Not Applicable

May 22, 2024

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Details:

AVP-786 (deudextromethorphan hydrobromide/quinidine sulfate) is a combinational a CYP2D6 inhibitor. It is being evaluated for the treatment of dementia due to Alzheimer’s disease.


Lead Product(s): Deudextromethorphan Hydrobromide,Quinidine sulphate

Therapeutic Area: Neurology Brand Name: AVP-786

Study Phase: Phase IIIProduct Type: Small molecule

Sponsor: Not Applicable

Deal Size: Not Applicable Upfront Cash: Not Applicable

Deal Type: Not Applicable February 12, 2024

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02

CPHI Middle east
Not Confirmed
CPHI Middle east
Not Confirmed

Details : AVP-786 (deudextromethorphan hydrobromide/quinidine sulfate) is a combinational a CYP2D6 inhibitor. It is being evaluated for the treatment of dementia due to Alzheimer’s disease.

Brand Name : AVP-786

Molecule Type : Small molecule

Upfront Cash : Not Applicable

February 12, 2024

blank

Details:

Avanir and Otsuka have always shared a deep commitment to advancing solutions that improve the lives of patients by Nuedexta (dextromethorphan hydrobromide and quinidine sulfate).


Lead Product(s): Deudextromethorphan Hydrobromide,Quinidine sulphate

Therapeutic Area: Neurology Brand Name: AVP-786

Study Phase: Phase IIIProduct Type: Small molecule

Sponsor: Otsuka America Pharmaceutical, Inc.

Deal Size: Undisclosed Upfront Cash: Undisclosed

Deal Type: Merger October 24, 2022

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03

CPHI Middle east
Not Confirmed
CPHI Middle east
Not Confirmed

Details : Avanir and Otsuka have always shared a deep commitment to advancing solutions that improve the lives of patients by Nuedexta (dextromethorphan hydrobromide and quinidine sulfate).

Brand Name : AVP-786

Molecule Type : Small molecule

Upfront Cash : Undisclosed

October 24, 2022

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