[go: up one dir, main page]

WO2017066730A1 - Nouvelles méthodes - Google Patents

Nouvelles méthodes Download PDF

Info

Publication number
WO2017066730A1
WO2017066730A1 PCT/US2016/057253 US2016057253W WO2017066730A1 WO 2017066730 A1 WO2017066730 A1 WO 2017066730A1 US 2016057253 W US2016057253 W US 2016057253W WO 2017066730 A1 WO2017066730 A1 WO 2017066730A1
Authority
WO
WIPO (PCT)
Prior art keywords
azabicyclo
methylphenyl
hexane
pharmaceutically acceptable
acceptable salt
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2016/057253
Other languages
English (en)
Inventor
Anthony Mckinney
Franklin Bymaster
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
EBI LIFE SCIENCES Inc
Original Assignee
EBI LIFE SCIENCES Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by EBI LIFE SCIENCES Inc filed Critical EBI LIFE SCIENCES Inc
Publication of WO2017066730A1 publication Critical patent/WO2017066730A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/439—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/20—Hypnotics; Sedatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present disclosure relates to novel methods for the treatment or prophylaxis of pain, depression, and/or anxiety in an equine in need thereof comprising administering to the equine an effective amount of l-(4-methylphenyl)-3-azabicyclo[3.1.0]hexane, in free or pharmaceutically acceptable salt form.
  • Pain and anxiety management may be especially important with orthopedic injuries in horses because if the horse is agitated the injury can easily be aggravated, potentially leading to permanent disability and even death.
  • NSAIDs non-steroidal anti-inflammatory drugs
  • COX cyclooxygenase
  • Certain prostaglandins activate prostaglandin receptors throughout the body, producing pain, inflammation, and fever.
  • other prostaglandins are responsible for protecting the stomach and intestinal lining from acid and digestive enzymes and for regulating renal blood flow and maintaining normal renal tubular function.
  • NSAIDs can decrease production of prostaglandins involved in inflammation, but can also decrease production of prostaglandins that protect organs. Accordingly, gastric ulcers can result from NSAID use.
  • NSAIDs also have a number of other disadvantages for use in equines, particularly with long-term use. For instance, problems with NSAIDs include reduction in bone remodeling, colic, kidney damage, particularly in horses that are dehydrated and young and old horses, and diarrhea. NSAIDs are particularly dangerous in foals because their kidney function is not fully developed and because they are especially sensitive to the intestinal side effects.
  • Opioids may also be used to manage pain in horses, however, opioids have a number of disadvantages in this species as well. Problems with opioids include the special licensing and record keeping required; predisposition to ileus, constipation, and colic; and production of excitement (increased locomotor activity), agitation, disorientation, and ataxia. In addition, opioids may cause disorientation which may aggravate an injury, with potentially catastrophic consequences. Urine retention may result from large or repeated dosages of opioids which is an important postsurgical consideration in some horses.
  • a method of treating pain in an equine in need thereof comprising administering to the equine an effective amount of l-(4-methylphenyl)-3- azabicyclo[3.1.0]hexane (bicifadine), in free or pharmaceutically acceptable salt form.
  • Also provided is a method of treating depression in an equine in need thereof comprising administering to the equine an effective amount of l-(4-methylphenyl)-3- azabicyclo[3.1.0]hexane (bicifadine), in free or pharmaceutically acceptable salt form.
  • a method of treating anxiety e.g., separation anxiety and/or generalized anxiety disorder
  • an equine in need thereof comprising administering to the equine an effective amount of l-(4-methylphenyl)-3-azabicyclo[3.1.0]hexane (bicifadine), in free or pharmaceutically acceptable salt form.
  • ranges are used as shorthand for describing each and every value that is within the range. Any value within the range can be selected as the terminus of the range.
  • U.S. Patent No. 7,094,799 describes l-(4-methylphenyl)-3-azabicyclo[3.1.0]hexane hydrochloride as a non-narcotic analgesic.
  • the use of l-(4-methylphenyl)-3- azabicyclo[3.1.OJhexane to treat pain in an equine in need thereof has not been previously disclosed.
  • l-(4-methylphenyl)-3-azabicyclo[3.1. OJhexane is a serotonin-norepinephrine- dopamine reuptake inhibitor.
  • l-(4-methylphenyl)-3-azabicyclo[3.1. OJhexane is believed to be metabolized with a dual extrahepatic (MAO) and hepatic (cytochrome) metabolism. This dual non-renal mechanism of metabolism may relieve stress on the kidneys, especially in a horse with other causes of renal dysfunction (e.g., exertional rhabdomyolysis).
  • MAO extrahepatic
  • cytochrome hepatic
  • This dual non-renal mechanism of metabolism may relieve stress on the kidneys, especially in a horse with other causes of renal dysfunction (e.g., exertional rhabdomyolysis).
  • OJhexane may not significantly inhibit cyclooxygenase in equines, use of l-(4-methylphenyl)-3-azabicyclo[3.1. OJhexane may be less detrimental to the stomach and colon compared to NSAIDs. Long-term use of NSAIDs, for example with a soft tissue injury, can result in ulcers.
  • anti-inflammatory activity is not necessarily desired with an orthopedic injury in a horse, because the anti-inflammatory activity may give the practitioner false belief that the injury has been cured leading an owner to push the horse and causing the horse further injury, potentially leading to a catastrophic outcome. Similar masking may also occur with colic.
  • l-(4-methylphenyl)-3-azabicyclo[3.1.0]hexane has analgesic properties without classic anti-inflammatory activity.
  • 5-HT serotonin
  • a method of treating pain in an equine in need thereof comprising administering to the equine an effective amount of l-(4-methylphenyl)-3- azabicyclo[3.1.0]hexane, in free or pharmaceutically acceptable salt form.
  • l-(4-methylphenyl)-3-azabicyclo[3.1.0]hexane may be synthesized as described in U.S. Patent Nos. 4, 131,611 and 4,435,419.
  • l-(4-methylphenyl)-3-azabicyclo[3.1.0]hexane is to be understood as embracing the compound in any form, for example, free or pharmaceutically acceptable salt form, e.g., as a pharmaceutically acceptable acid addition salt.
  • Pharmaceutically acceptable salts are known in the art and include salts that are physiologically acceptable at the dosage amount and form to be administered, for example, hydrochloride salts.
  • Crystal form and “polymorph” may be used interchangeably herein, and are meant to include all crystalline forms of l-(4-methylphenyl)-3-azabicyclo[3.1.0]hexane, in free or pharmaceutically acceptable salt form, including, for example, solvates (including hydrates).
  • (+) and (-) enantiomers of l-(4-methylphenyl)-3-azabicyclo[3.1.0]hexane are described by Epstein et al., Journal of Medicinal Chemistry, 1981, 24 (5), 481. See also U.S. Patent Nos. 4, 131,611, 4,231,935, and 4,435,419. In some embodiments, an effective amount of (+)-l-(4-methylphenyl)-3-azabicyclo[3.1.0]hexane, in free or pharmaceutically acceptable salt form, is used.
  • an effective amount of (-)-l-(4-methylphenyl)-3- azabicyclo[3.1.0]hexane, in free or pharmaceutically acceptable salt form is used.
  • a mixture of (+)-l-(4-methylphenyl)-3-azabicyclo[3.1.0]hexane, in free or pharmaceutically acceptable salt form, and (-)-l-(4-methylphenyl)-3-azabicyclo[3.1.0]hexane, in free or pharmaceutically acceptable salt form is used (e.g., a racemic mixture, a mixture comprising > 50% (+)-l-(4-methylphenyl)-3-azabicyclo[3.1.0]hexane, in free or
  • an effective amount comprises essentially pure (+)-l-(4- methylphenyl)-3-azabicyclo[3.1.0]hexane, in free or pharmaceutically acceptable salt form (e.g., having 90-95%) of (+)-l-(4-methylphenyl)-3-azabicyclo[3.1.0]hexane, in free or pharmaceutically acceptable salt form, by weight of total l-(4-methylphenyl)-3- azabicyclo[3.1.0]hexane, in free or pharmaceutically acceptable salt form, present), essentially pure (-)-l-(4-methylphenyl)-3-azabicyclo[3.1.0]hexane, in free or
  • l-(4-methylphenyl)-3-azabicyclo[3.1.0]hexane hydrochloride exists in at least two polymorphic forms, labeled polymorphs A and B as disclosed in U.S. Patent No. 7,094,799, which is hereby incorporated by reference in its entirety. Crystalline and amorphous forms of l-(4-methylphenyl)-3-azabicyclo[3.1.0]hexane, in free or pharmaceutically acceptable salt form, may be used in any combination or in forms that are substantially free of one or more of the other crystalline forms or free of the amorphous form.
  • useful forms of l-(4-methylphenyl)-3-azabicyclo[3.1.0]hexane within the methods, uses, and compositions described herein include l-(4-methylphenyl)-3- azabicyclo[3.1.0]hexane, in free or pharmaceutically acceptable salt form, as well as enantiomers, polymorphs, solvates, hydrates, prodrugs, and combinations thereof.
  • l-(4-methylphenyl)-3-azabicyclo[3.1.0]hexane also encompasses its stable and unstable isotopes.
  • Stable isotopes are nonradioactive isotopes that contain one additional neutron compared to the abundant nuclides of the same species (i.e., element).
  • the hydrogen atom at a certain position on l-(4-methylphenyl)-3-azabicyclo[3.1.0]hexane may be replaced with deuterium (a stable isotope which is non-radioactive).
  • unstable isotopes which are radioactive isotopes that contain additional neutrons compared to the abundant nuclides of the same species (i.e., element), e.g., C, may replace the corresponding abundant species.
  • an effective amount comprises at least 10% to 10-20%, 20- 35%, 35-50%, 50-70%, 70-85%, 85-95%, and up to 95-99% or greater (by weight) polymorph B.
  • substantially free of other polymorphic forms means that the crystalline material, e.g., polymorph A or polymorph B, contains 10% w/w or less of any other crystalline form.
  • a crystalline material, e.g., polymorph A or polymorph B contains 5% w/w or less of any other crystalline form, e.g., 1% w/w or less of any other crystalline form.
  • treatment and “treating” include minimizing or eliminating pain in an equine.
  • ⁇ ективное amount is intended to encompass a therapeutically effective amount to treat a specific disease or disorder.
  • equivalent refers to animals belonging to the family Equidae including, for example, horses, ponies, miniature horses, miniature ponies, donkeys, mules, and zebras.
  • pain includes pain of varying severity, i.e. mild, moderate, and severe pain, as well as acute and chronic pain.
  • pain occurs because of an injury (e.g., an orthopedic injury, e.g., a bone fracture or contusion), degenerative issues in the animal's tissues, blunt trauma, or following surgery or medical treatment.
  • pain occurs because of a soft tissue injury, such as an injury to a ligament or tendon.
  • the pain is associated with colic in the equine.
  • colic encompasses all forms of gastrointestinal conditions which cause pain as well as other causes of abdominal pain not involving the gastrointestinal tract. Colic may include a visceral component.
  • the pain is associated with laminitis in the equine, e.g., acute laminitis or chronic laminitis.
  • the pain is due to arthritis, for example osteoarthritis (also known as degenerative joint disease).
  • acute pain refers to either an initial phase of a painful condition that either largely resolves within several hours, days, or months (typically lasting no more than 3 months) or progresses on to a subacute pain (e.g., lasting 3-6 months) or chronic pain (e.g., persisting, in some cases intermittently, for more than 3 months, and often more than 6 months).
  • Acute pain also refers to a transient exacerbation or flare up of a chronic pain condition in which pain intensity worsens substantially, whereby supplemental treatment and/or upwards dose adjustment is indicated, provided that such treatment would be tolerated adequately.
  • Acute pain may occur with or after colic, fracture, trauma, surgery, infection, or inflammatory disease.
  • chronic pain refers to pain that lasts more than 3 months, for example more than 6 months, and/or extends beyond the expected period of healing. Chronic pain may be considered pathologic, or having the characteristics of a diseased state. It may be unrelenting, have no identifiable cause, spread beyond the original site of an injury or insult, and serve no biological function.
  • Chronic pain may occur with musculoskeletal injury or disease (e.g., chronic pain may occur with laminitis, osteoarthritis, stomatitis, and intervertebral disk disease). Chronic pain may also include pain consequent to cancer, diabetes, and chronic low back pain.
  • chronic pain may occur with laminitis, osteoarthritis, stomatitis, and intervertebral disk disease. Chronic pain may also include pain consequent to cancer, diabetes, and chronic low back pain.
  • neuroopathic pain refers to pain caused by injury or damage to either the peripheral and/or the central nervous system.
  • composition As used herein, “concurrently” means the compounds are administered simultaneously or within the same composition. In some embodiments, the compounds are administered simultaneously. In some embodiments, the compounds are administered within the same composition.
  • a foal is a young equine (e.g., horse), for example, an equine (e.g., horse) that is one year old or younger.
  • Method 1 for the treatment or prophylaxis of pain in an equine in need thereof comprising administering to the equine an effective amount of l-(4- methylphenyl)-3-azabicyclo[3.1.0]hexane, in free or pharmaceutically acceptable salt form.
  • Method 2 for the treatment or prophylaxis of depression in an equine in need thereof comprising administering to the equine an effective amount of l-(4-methylphenyl)-3-azabicyclo[3.1.0]hexane, in free or pharmaceutically acceptable salt form.
  • Method 3 for the treatment or prophylaxis of anxiety (e.g., separation anxiety and/or generalized anxiety disorder) in an equine in need thereof comprising administering to the equine an effective amount of l-(4-methylphenyl)-3- azabicyclo[3.1.0]hexane, in free or pharmaceutically acceptable salt form.
  • anxiety e.g., separation anxiety and/or generalized anxiety disorder
  • Method 1 e.g., Method 1
  • Method 2 e.g., Method 3
  • Method 1 Any one of Methods 1, 2, or 3, e.g., Method 1, e.g., Method 2, e.g., Method 3,
  • a pharmaceutically acceptable salt form comprising administering 0.5 to 50 mg/kg/day, e.g., 1 to 50 mg/kg/day, e.g., 2 to 45 mg/kg/day, e.g., 5 to 40 mg/kg/day, e.g., 10 to 35 mg/kg/day, e.g., 15 to 30 mg/kg/day, e.g., 15 to 25 mg/kg/day, of l-(4-methylphenyl)-3-azabicyclo[3.1.0]hexane, in free or pharmaceutically acceptable salt form.
  • 0.5 to 50 mg/kg/day e.g., 1 to 50 mg/kg/day, e.g., 2 to 45 mg/kg/day, e.g., 5 to 40 mg/kg/day, e.g., 10 to 35 mg/kg/day, e.g., 15 to 30 mg/kg/day, e.g., 15 to 25 mg/kg/day, of l-(4
  • Methods 1, 2, or 3 e.g., Method 1, e.g., Method 2, e.g., Method 3, or 1.1 comprising administering l-(4-methylphenyl)-3-azabicyclo[3.1.0]hexane, in free or pharmaceutically acceptable salt form, once or twice daily.
  • Methods 1, 2, or 3 e.g., Method 1, e.g., Method 2, e.g., Method 3, or 1.1 or 1.2 wherein l-(4-methylphenyl)-3-azabicyclo[3.1.0]hexane, in free or
  • Methods 1, 2, or 3 e.g., Method 1, e.g., Method 2, e.g., Method 3, or 1.1-
  • Methods 1, 2, or 3 e.g., Method 1, e.g., Method 2, e.g., Method 3, or 1.1-
  • Methods 1, 2, or 3 e.g., Method 1, e.g., Method 2, e.g., Method 3, or 1.1-
  • l-(4-methylphenyl)-3-azabicyclo[3.1.0]hexane in pharmaceutically acceptable salt form is l-(4-methylphenyl)-3-azabicyclo[3.1.0]hexane hydrochloride.
  • Method 1.6 wherein l-(4-methylphenyl)-3-azabicyclo[3.1.0]hexane hydrochloride is l-(4-methylphenyl)-3-azabicyclo[3.1.0]hexane hydrochloride polymorph form B.
  • Method 1.7 wherein l-(4-methylphenyl)-3-azabicyclo[3.1.0]hexane hydrochloride polymorph form B is substantially free of other polymorphic forms.
  • Method 1.6 wherein l-(4-methylphenyl)-3-azabicyclo[3.1.0]hexane hydrochloride is l-(4-methylphenyl)-3-azabicyclo[3.1.0]hexane hydrochloride polymorph form A.
  • Method 1.9 wherein l-(4-methylphenyl)-3-azabicyclo[3.1.0]hexane hydrochloride polymorph form A is substantially free of other polymorphic forms.
  • Methods 1, 2, or 3 e.g., Method 1, e.g., Method 2, e.g., Method 3, or 1.1- 1.6 comprising administering an effective amount of (+)-l-(4-methylphenyl)-3- azabicyclo[3.1.0]hexane, in free or pharmaceutically acceptable salt form.
  • Methods 1, 2, or 3 e.g., Method 1, e.g., Method 2, e.g., Method 3, or 1.1- 1.6 comprising administering an effective amount of (-)-l-(4-methylphenyl)-3- azabicyclo[3.1.0]hexane, in free or pharmaceutically acceptable salt form.
  • Methods 1, 2, or 3 e.g., Method 1, e.g., Method 2, e.g., Method 3, or 1.1-
  • 1.12 further comprising administering one or more of a local anesthetic, an opioid, an alpha-2 agonist, a non-steroidal anti-inflammatory drug (NSAID), a corticosteroid, a N-methyl-D-aspartate (NMD A) receptor antagonist, a NK1 receptor antagonist, a calcium channel blocker, a muscle relaxant, and a bisphosphonate.
  • NSAID non-steroidal anti-inflammatory drug
  • a corticosteroid a corticosteroid
  • N-methyl-D-aspartate (NMD A) receptor antagonist a NK1 receptor antagonist
  • a calcium channel blocker a muscle relaxant
  • a bisphosphonate a bisphosphonate
  • Methods 1, 2, or 3 e.g., Method 1, e.g., Method 2, e.g., Method 3, or 1.1-
  • 1.13 further comprising administering one or more of procaine, chloroprocaine, mepivacaine, prilocaine, lidocaine, articaine, tetracaine, bupivacaine (with or without epinephrine), levobupivacaine, ropivacaine, capsaicin, resiniferatoxin, morphine, oxymorphone, meperidine, methadone, hydromorphone, fentanyl, butorphanol, codeine (e.g., codeine/acetaminophen), hydrocodone, tramadol, buprenorphine, alfentanil, sufentanil, pentazocine, nalbuphine, naloxone, nalmefene, xylazine, detomidine, medetomidine, dexmedetomidine, romifidine, aspirin, acetaminophen, phenylbutazone, flunixin (
  • Methods 1, 2, or 3 e.g., Method 1, e.g., Method 2, e.g., Method 3, or 1.1-
  • 1.15 further comprising performing one or more of acupuncture, rehabilitation, low- level laser, transcutaneous electric nerve stimulation, hydrotherapy, massage, prolotherapy, neural therapy, and reflexology.
  • Methods 1, 2, or 3 e.g., Method 1, e.g., Method 2, e.g., Method 3, or 1.1-
  • 1.16 further comprising administering one or more of a nutraceutical and an herbal supplement.
  • Any one of Methods 3 or 1.1-1.19 or 1.24 wherein the anxiety is separation anxiety. Any one of Methods 3 or 1.1-1.19 or 1.24 wherein the anxiety is generalized anxiety disorder.
  • Methods 2 or 1.1-1.19 wherein the depression is co-morbid with pain 1.32 Method 1.31 wherein the pain is acute pain.
  • Methods 1, 2, or 3 e.g., Method 1, e.g., Method 2, e.g., Method 3, or 1.1- 1.34 wherein the equine is a horse.
  • Method 1.35 wherein the horse is a racehorse (e.g., a thoroughbred racehorse).
  • a racehorse e.g., a thoroughbred racehorse
  • Methods 1, 2, or 3 e.g., Method 1, e.g., Method 2, e.g., Method 3, or 1.1- 1.37 wherein the equine is a foal (e.g., a foal horse).
  • a foal e.g., a foal horse
  • Methods 1, 2, or 3 e.g., Method 1, e.g., Method 2, e.g., Method 3, or 1.1-
  • composition comprising an effective amount of l-(4-methylphenyl)-3- azabicyclo[3.1.0]hexane, in free or pharmaceutically acceptable salt form, in combination with a pharmaceutically acceptable diluent or carrier.
  • Methods 1, 2, or 3 e.g., Method 1, e.g., Method 2, e.g., Method 3, or 1.1-
  • composition consisting essentially of an effective amount of l-(4-methylphenyl)-3- azabicyclo[3.1.0]hexane, in free or pharmaceutically acceptable salt form, in combination with a pharmaceutically acceptable diluent or carrier.
  • the active agent(s) and 1- (4-methylphenyl)-3-azabicyclo[3.1.0]hexane, in free or pharmaceutically acceptable salt form may be administered concurrently or sequentially in any order.
  • l-(4-methylphenyl)-3-azabicyclo[3.1.0]hexane in free or pharmaceutically acceptable salt form, for the treatment or prophylaxis of pain, depression, and/or anxiety in an equine in need thereof, for example, for use in any one of Methods 1, 2, or 3, e.g., Method 1, e.g., Method 2, e.g., Method 3, e.g., any one of Methods 1.1-1.40.
  • l-(4-methylphenyl)-3-azabicyclo[3.1.0]hexane in free or pharmaceutically acceptable salt form, in the manufacture of a medicament for the treatment or prophylaxis of pain, depression, and/or anxiety in an equine in need thereof, for example, for use in any one of Methods 1, 2, or 3, e.g., Method 1, e.g., Method 2, e.g., Method 3, e.g., any one of Methods 1.1-1.40.
  • compositions comprising an effective amount of 1- (4-methylphenyl)-3-azabicyclo[3.1.0]hexane, in free or pharmaceutically acceptable salt form, in combination with a pharmaceutically acceptable diluent or carrier, for use in the treatment or prophylaxis of pain, depression, and/or anxiety in an equine in need thereof, for example, for use in any one of Methods 1, 2, or 3, e.g., Method 1, e.g., Method 2, e.g., Method 3, e.g., any one of Methods 1.1-1.40.
  • compositions consisting essentially of an effective amount of l-(4-methylphenyl)-3-azabicyclo[3.1.0]hexane, in free or pharmaceutically acceptable salt form, in combination with a pharmaceutically acceptable diluent or carrier, for use in the treatment or prophylaxis of pain, depression, and/or anxiety in an equine in need thereof, for example, for use in any one of Methods 1, 2, or 3, e.g., Method 1, e.g., Method 2, e.g., Method 3, e.g., any one of Methods 1.1-1.40.
  • a dose or method of administration of the dose of the present disclosure is not particularly limited. Dosages employed will vary depending, e.g., on the particular disease or condition to be treated, the mode of administration, and the therapy desired. l-(4- methylphenyl)-3-azabicyclo[3.1.0]hexane, in free or pharmaceutically acceptable salt form, may be administered by any suitable route, including orally, parenterally, transdermally, or by inhalation, although various other known delivery routes, devices and methods can likewise be employed.
  • compositions comprising l-(4-methylphenyl)-3- azabicyclo[3.1.0]hexane, in free or pharmaceutically acceptable salt form, may be prepared using conventional diluents or excipients and techniques known in the galenic art.
  • dosage forms may include tablets, capsules, solutions, suspensions, pastes, and the like.

Landscapes

  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Epidemiology (AREA)
  • Pain & Pain Management (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Hospice & Palliative Care (AREA)
  • Anesthesiology (AREA)
  • Psychiatry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne de nouvelles méthodes pour le traitement ou la prophylaxie de la douleur chez un équidé en ayant besoin, consistant à administrer à l'équidé une quantité efficace de 1-(4-méthylphényl)-3-azabicyclo [3.1.0] hexane, sous forme libre ou de sel pharmaceutiquement acceptable.
PCT/US2016/057253 2015-10-16 2016-10-16 Nouvelles méthodes Ceased WO2017066730A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201562242959P 2015-10-16 2015-10-16
US62/242,959 2015-10-16

Publications (1)

Publication Number Publication Date
WO2017066730A1 true WO2017066730A1 (fr) 2017-04-20

Family

ID=58518133

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2016/057253 Ceased WO2017066730A1 (fr) 2015-10-16 2016-10-16 Nouvelles méthodes

Country Status (1)

Country Link
WO (1) WO2017066730A1 (fr)

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050282859A1 (en) * 2004-06-04 2005-12-22 Thor Karl B Dual acting SNRI-NMDA antagonists for the treatment of genitourinary disorders

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050282859A1 (en) * 2004-06-04 2005-12-22 Thor Karl B Dual acting SNRI-NMDA antagonists for the treatment of genitourinary disorders

Similar Documents

Publication Publication Date Title
US11147799B2 (en) Topical pharmaceutical composition containing phenytoin and a (co-) analgesic for the treatment of chronic pain
Lamont Adjunctive analgesic therapy in veterinary medicine
DK2488170T3 (en) FORMATIONS comprising tramadol and celecoxib, FOR THE TREATMENT OF PAIN
JP6336592B2 (ja) ヒスタミンｈ４受容体を介してもたらされた掻痒状態を治療するための医薬組成物
US12257233B2 (en) Methods
US20240285576A1 (en) R-mdma for treatment of pain
JP2017534613A (ja) デクスメデトミジン製剤を使用する睡眠障害の予防または治療
CN106456637B (zh) (s)-吡吲哚及其药学上可接受的盐的药学用途
CN102395358A (zh) Nk受体拮抗剂的用途
JP2005533784A (ja) 吐き気および嘔吐の治療のためのネフォパムの使用
CN1897956A (zh) 用于治疗肌纤维痛的方法和含有沙利度胺的组合物
CN106413714A (zh) (r)‑吡吲哚及其药学上可接受的盐的药学用途
WO2017066730A1 (fr) Nouvelles méthodes
JP2025036479A (ja) 疼痛、炎症および／または自己免疫の処置または予防における使用のための化合物
CN114599649B (zh) 用于预防和/或治疗哺乳动物的过度疲劳的化合物
CN113811297A (zh) 用于预防和/或治疗动物中的疼痛的4-[5-[(rac)-1-[5-(3-氯苯基)-3-异噁唑基]乙氧基]-4-甲基-4H-1,2,4-三唑-3-基]吡啶
Thanoon et al. Evaluation the combination of chlorpheniramine and tramadol at a level of thermal and visceral antinociceptive in a mouse acute pain model.
WO2017066729A1 (fr) Nouveaux procédés
Ramsay Use of analgesics in exotic felids
Walsh et al. Chemical analgesia for velvet antler removal in deer
JP7090344B2 (ja) セロトニン３受容体アゴニストによる疼痛の治療
JP2010509294A5 (fr)
HK40071826A (en) Compound for use in prevention and/or treatment of surmenage in a mammal
US20090270400A1 (en) Painkilling association comprising a dihydroimidazopyrazine derivative
US20210393553A1 (en) Pharmaceutical combinations for the treatment of pain

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 16856381

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

32PN Ep: public notification in the ep bulletin as address of the adressee cannot be established

Free format text: NOTING OF LOSS OF RIGHTS PURSUANT TO RULE 112(1) EPC (EPO FORM 1205A DATED 10/08/2018)

122 Ep: pct application non-entry in european phase

Ref document number: 16856381

Country of ref document: EP

Kind code of ref document: A1