Use of flecainide as an anti-connexin agent and method for potentiating the effects of a psychotropic drug

• US 9,750,734 B2
• Filed: 07/24/2014
• Issued: 09/05/2017
• Est. Priority Date: 07/24/2013
• Status: Active Grant

• Current Assignee: Commissariat a L'Energie Atomique (French Alternative Energies and Atomic Energy Commission)
• Original Assignee: Commissariat a L'Energie Atomique (French Alternative Energies and Atomic Energy Commission)
• Inventors: Mouthon, Franck, Charveriat, Mathieu
• Primary Examiner(s): HUI, SAN MING R
• Application Number:
  US14/907,221
• Publication Number:
  US 20160158213A1
• Time in Patent Office: 1,139 Days
• Field of Search: 514331, 514618
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 31/4458 only substituted in position 2, e.g. methylphenidate
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/12 Antidiarrhoeals
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/10 for impotence
• CPC Class Codes: A61P 15/12 for climacteric disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/20 : Hypnotics; Sedatives
• CPC Class Codes: A61P 25/22 : Anxiolytics
• CPC Class Codes: A61P 25/24 : Antidepressants
• CPC Class Codes: A61P 25/26 : Psychostimulants, e.g. nicotine, cocaine
• CPC Class Codes: A61P 25/28 : for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 25/30 : for treating abuse or dependence
• CPC Class Codes: A61P 27/16 : Otologicals
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/02 : Nutrients, e.g. vitamins, minerals
• CPC Class Codes: A61P 3/04 : Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 31/12 : Antivirals
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

The present invention relates to the use of flecainide as an anti-connexin agent. This anti-connexin agent is advantageously used to potentiate the therapeutic effect of various psychotropic drugs. More specifically, the invention provides a combination product containing flecainide and modafinil.

Claims

1. A therapeutic composition comprising flecainide and at least one psychotropic drug, wherein said at least one psychotropic drug is modafinil.

2. A method for treating fatigue, somnolence, or sleepiness in an individual in need thereof comprising administration of the therapeutic composition according to claim 1 to said individual.

3. A method for at least one of enhancing the memory of healthy subjects or maintaining said healthy subjects awake for long-lasting periods of time comprising administration of the therapeutic composition of claim 1 to said healthy subjects.

4. A method for treating cataplexy in a narcoleptic patient comprising administration of the therapeutic composition according to claim 1 to said narcoleptic patient.

5. The therapeutic composition of claim 1, wherein said flecainide is the R enantiomer of formula:

7. The method of claim 2, wherein said flecainide is the R enantiomer of formula:

11. The method of claim 2, wherein said flecainide in said therapeutic composition is the R enantiomer of formula:

12. The method of claim 3, wherein said flecainide in said therapeutic composition is the R enantiomer of formula:

13. The method of claim 4, wherein said flecainide in said therapeutic composition is the R enantiomer of formula:

18. The method of claim 2 wherein the individual is suffering from excessive daytime sleepiness (EDS), sleep disorders, insufficient sleep time, central sleep apnea, narcolepsy with cataplexy, narcolepsy without cataplexy, obstructive sleep apnea/hypopnea (SAHOS), idiopathic hypersomnia, Kleine-Levin syndrome, circadian rhythm disorders, shift work sleep disorder, jet-lag, disorders after sleep restriction or sleep deprivation, attention disorders, alertness disorders, insomnia, parasomnia, medical-induced somnolence, restless legs syndrome (RLS), Periodic Lim Movement Disorders (PLMD), attention deficit hyperactivity disorder (ADHD), post-traumatic stress disorder (PTSD), Parkinson disease, multiple sclerosis, stroke, neuromuscular disorders, structural brain disorders, respiratory disorders, chronic renal failure, liver failure, rheumatologic disorders, mood disorders, anxiety disorders, schizophrenia, tinnitus, depression, malaise, dementia, bipolar disorder, obesity, hyperphagia, manic episode, obsessive-compulsive disorder, senility, dependence or addiction, cancer, neurodegenerative disorders, menopause, traumatic brain injuries, viral infection or post-myelitis, or fibromyalgia.

19. The method of claim 18, for treating cataplexy in narcoleptic patients.

20. The method of claim 19, wherein said flecainide is the R enantiomer of formula:

21. The method of claim 2 wherein the flecainide and modafinil are administered simultaneously, separately or in a staggered manner.

22. The method of claim 18 wherein the flecainide and modafinil are administered simultaneously, separately or in a staggered manner.

6. A method for enhancing the memory of healthy subjects and/or for maintaining them awake for long-lasting periods of time comprising the administration to said healthy subjects of a) flecainide and b) modafinil, in which said compounds a) and b) are administered simultaneously, separately or in a staggered manner.

14. The method of claim 6, wherein said flecainide is the R enantiomer of formula:

8. A method for potentiating the effects of modafinil, comprising the administration of flecainide as an anti-connexin agent.

9. The method of claim 8, wherein potentiating the effects of modafinil further comprises potentiating the promnesiant effect and/or the awakening effect of modafinil.

10. The method of claim 8, wherein said flecainide is the R enantiomer of formula:

15. The method of claim 8, wherein potentiating the effects of modafinil further comprises increasing at least one of the efficacy, safety, or duration of the action of modafinil.

16. The method of claim 15, wherein said flecainide is the R enantiomer of formula:

17. The method of claim 9, wherein said flecainide is the R enantiomer of formula: