WO1988009605A2 - Traitement de lesions cerebrales traumatiques et ischemiques avec des antagonistes de recepteurs d'opiaces - Google Patents

Traitement de lesions cerebrales traumatiques et ischemiques avec des antagonistes de recepteurs d'opiaces Download PDF

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Publication number
WO1988009605A2
WO1988009605A2 PCT/US1988/001839 US8801839W WO8809605A2 WO 1988009605 A2 WO1988009605 A2 WO 1988009605A2 US 8801839 W US8801839 W US 8801839W WO 8809605 A2 WO8809605 A2 WO 8809605A2
Authority
WO
WIPO (PCT)
Prior art keywords
opiate
receptor
traumatic
brain injury
receptor antagonist
Prior art date
Application number
PCT/US1988/001839
Other languages
English (en)
Inventor
Alan I. Faden
Original Assignee
Medicis Corporation
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 Medicis Corporation filed Critical Medicis Corporation
Publication of WO1988009605A2 publication Critical patent/WO1988009605A2/fr

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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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Definitions

  • Endogenous opioids may be released following traumatic or ischemic injury of the central nervous system. These opioids may serve as secondary pathophy ⁇ iologic factors contributing to the neurological disorder which stems fro"m the injury to the central nervous system.
  • Opiate receptor antagonists such as naloxone, has been used to treat brain or spinal cord injury at dosages in the range of 1 to 10 g/kg of body weight of the patient.
  • naloxone is not completely selective nor a pure opiate antagonist in all situations. At low dosages, naloxone has considerable selectivity for the mu-opiate receptor. At higher dosages, naloxone acts on other opiate receptors, including the delta and kappa receptors. Further at higher dosages, naloxone may have effects that are not mediated by opiate receptors.
  • opiate receptor antagonists v/hich exhibit a high degree of specificity for or enhanced activity at a specific opiate receptor are being sought. Also, opiate receptor antagonists which act exclusively as such without producing any undesirable side reactions within the body are preferred.
  • the present invention provides a method of inducing opiate-receptor antagonistic activity in a patient suffering from ischemic or traumatic brain injury which comprises administering to said patient an effective amount of an opiate-receptor antagonist having enhanced activity at the kappa-opiate receptor suitable to permit the induction of opiate-receptor antagonistic activity.
  • an opiate-receptor antagonist of the present invention there is contemplated any pharmaceutically acceptable compound or salt thereof having enhanced activity at the kappa-opiate receptor capable of inducing opiate receptor antagonistic activity.
  • an effective amount of the opiate-receptor antagonist of the present invention there is contemplated an amount of antagonist which is sufficient to induce opiate receptor antagonistic activity.
  • An effective amount of the opiate receptor antagonist of the present invention is from about 0.01 to about 10 mg/kg body weight of the patient daily.
  • a preferred embodiment of the present invention involves an effective amount of the opiate receptor antagonist from about 0.1 to 1 mg/kg body weight of the patient daily.
  • the opiate receptor antagonist of the present invention may be administered to the patient in any dosage form convenient under the patient's specific circumstances. Usually, parenteral administration is preferred.
  • a dosage unit suitable for intravenous administration which comprises (i) an effective amount of an opiate receptor antagonist having enhanced activity at or specificity for the kappa opiate receptor and (ii) a pharmaceutically acceptable solution.
  • a pharmaceutically acceptable solution there is contemplated any solution which is safe for injection and which is biologically inert and hence does not interfere with, the active ingredient.
  • a pharmaceuti ally acceptable solution may be mentioned an i ⁇ otonic solution suitable for injection into a patient.
  • the isotonic solution may contain water, salt and conventional ingredients such as glucose.
  • a preferred embodiment of the present invention provides a method of inducing opiate-receptor antagonistic activity in a patient suffering from ischemic or traumatic brain injury, wherein the opiate receptor antagonist administered to the patient is 3- (2-alpha, 6-alpha , US*) - (-) -1- cyclopentyl-5-(l,2,3,4,5, 6-hexahydro-8-hydroxy-3 ,6,11- trimethyl-2 , 6-methano-3-benzazocin-ll-yl) -3-pentanone methane sulfonate.
  • a further preferred embodiment of the present invention provides a method of inducing opiate-receptor antagonistic activity in a patient suffering from ischemic or traumatic brain injury, wherein said opiate-receptor antagonist is administered in a dosage of from about 0.04 to about 4 mg/kg 3-4 times daily.
  • a more preferred embodiment of the present invention provides a method of inducing opiate- receptor antagonistic activity in a patient suffering from ischemic or traumatic brain injury, wherein said opiate- receptor antagonist is administered in a dosage of from about 0.1 to about 1 mg/kg 3-4 times daily.
  • EXAMPLE 3 Induction of opiate receptor antagonistic activity in a patient suffering from traumatic or ischemic brain injury is accomplished through injection of 0.1 mg/kg of the pharmaceutical preparation of Example 1 4 times daily for 1 day.
  • EXAMPLE 4 Induction of opiate receptor antagonistic activity in a patient suffering from traumatic or ischemic brain injuiy is accomplished through injection of 0.5 of the pharmaceutical preparation of Example 2 3 times daily for 1 day.

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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Urology & Nephrology (AREA)
  • Cardiology (AREA)
  • Vascular Medicine (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Epidemiology (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
PCT/US1988/001839 1987-06-05 1988-06-06 Traitement de lesions cerebrales traumatiques et ischemiques avec des antagonistes de recepteurs d'opiaces WO1988009605A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US5833787A 1987-06-05 1987-06-05
US058,337 1987-06-05

Publications (1)

Publication Number Publication Date
WO1988009605A2 true WO1988009605A2 (fr) 1988-12-15

Family

ID=22016198

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1988/001839 WO1988009605A2 (fr) 1987-06-05 1988-06-06 Traitement de lesions cerebrales traumatiques et ischemiques avec des antagonistes de recepteurs d'opiaces

Country Status (4)

Country Link
EP (1) EP0348440A1 (fr)
JP (1) JPH02500439A (fr)
CA (1) CA1322522C (fr)
WO (1) WO1988009605A2 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994013641A1 (fr) * 1992-12-16 1994-06-23 Japan Tobacco Inc. Utilisation de benzomorphane comme antagoniste du recepteur du nmda

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994013641A1 (fr) * 1992-12-16 1994-06-23 Japan Tobacco Inc. Utilisation de benzomorphane comme antagoniste du recepteur du nmda

Also Published As

Publication number Publication date
EP0348440A1 (fr) 1990-01-03
JPH02500439A (ja) 1990-02-15
CA1322522C (fr) 1993-09-28

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