MXPA00011509A - Method for the treatment of insomnia - Google Patents
Method for the treatment of insomniaInfo
- Publication number
- MXPA00011509A MXPA00011509A MXPA/A/2000/011509A MXPA00011509A MXPA00011509A MX PA00011509 A MXPA00011509 A MX PA00011509A MX PA00011509 A MXPA00011509 A MX PA00011509A MX PA00011509 A MXPA00011509 A MX PA00011509A
- Authority
- MX
- Mexico
- Prior art keywords
- formula
- gabapentin
- insomnia
- treatment
- gaba
- Prior art date
Links
- 206010022437 Insomnia Diseases 0.000 title claims abstract description 14
- BTCSSZJGUNDROE-UHFFFAOYSA-N GABA Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 claims abstract description 20
- 150000001875 compounds Chemical class 0.000 claims description 23
- UGJMXCAKCUNAIE-UHFFFAOYSA-N Gabapen Chemical compound OC(=O)CC1(CN)CCCCC1 UGJMXCAKCUNAIE-UHFFFAOYSA-N 0.000 claims description 22
- 229960002870 gabapentin Drugs 0.000 claims description 21
- 239000011780 sodium chloride Substances 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 8
- 125000004432 carbon atoms Chemical group C* 0.000 claims description 6
- AYXYPKUFHZROOJ-ZETCQYMHSA-N (3S)-3-(aminomethyl)-5-methylhexanoic acid Chemical compound CC(C)C[C@H](CN)CC(O)=O AYXYPKUFHZROOJ-ZETCQYMHSA-N 0.000 claims description 5
- 241000124008 Mammalia Species 0.000 claims description 5
- 229960001233 pregabalin Drugs 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 125000004435 hydrogen atoms Chemical group [H]* 0.000 claims description 2
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 2
- 229960003692 aminobutyric acid Drugs 0.000 abstract description 4
- 229940013945 gamma-Aminobutyric Acid Drugs 0.000 abstract description 4
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 abstract description 2
- 229960002989 Glutamic Acid Drugs 0.000 abstract 1
- 235000013922 glutamic acid Nutrition 0.000 abstract 1
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- DRLFMBDRBRZALE-UHFFFAOYSA-N melatonin Chemical compound COC1=CC=C2NC=C(CCNC(C)=O)C2=C1 DRLFMBDRBRZALE-UHFFFAOYSA-N 0.000 description 2
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- QOWAMIUFBNBINS-UHFFFAOYSA-N 2-[6-[4,5-diethoxy-2-(ethoxymethyl)-6-methoxyoxan-3-yl]oxy-4,5-dimethoxy-2-(methoxymethyl)oxan-3-yl]oxy-6-(hydroxymethyl)-5-methoxyoxane-3,4-diol Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(OC)C(OC)C(OC2C(C(O)C(OC)C(CO)O2)O)C(COC)O1 QOWAMIUFBNBINS-UHFFFAOYSA-N 0.000 description 1
- AYXYPKUFHZROOJ-UHFFFAOYSA-N 3-(azaniumylmethyl)-5-methylhexanoate Chemical compound CC(C)CC(CN)CC(O)=O AYXYPKUFHZROOJ-UHFFFAOYSA-N 0.000 description 1
- 229940005513 ANTIDEPRESSANTS Drugs 0.000 description 1
- 229940005529 ANTIPSYCHOTICS Drugs 0.000 description 1
- 229940005530 ANXIOLYTICS Drugs 0.000 description 1
- XJKJWTWGDGIQRH-BFIDDRIFSA-N Alginic acid Chemical compound O1[C@@H](C(O)=O)[C@@H](OC)[C@H](O)[C@H](O)[C@@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](C)[C@@H](O)[C@H]1O XJKJWTWGDGIQRH-BFIDDRIFSA-N 0.000 description 1
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- CZMRCDWAGMRECN-GDQSFJPYSA-N Sucrose Natural products O([C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O1)[C@@]1(CO)[C@H](O)[C@@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-GDQSFJPYSA-N 0.000 description 1
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- 210000001364 Upper Extremity Anatomy 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K [O-]P([O-])([O-])=O Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
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- 239000000935 antidepressant agent Substances 0.000 description 1
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- 230000001419 dependent Effects 0.000 description 1
- PCHPORCSPXIHLZ-UHFFFAOYSA-N diphenhydramine hydrochloride Chemical compound [Cl-].C=1C=CC=CC=1C(OCC[NH+](C)C)C1=CC=CC=C1 PCHPORCSPXIHLZ-UHFFFAOYSA-N 0.000 description 1
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Abstract
The instant invention is a method of using certain analogs of glutamic acid and gamma-aminobutyric acid to treat insomnia.
Description
METHOD FOR THE TREATMENT OF INSOMNIA
BACKGROUND OF THE INVENTION
FIELD OF THE INVENTION The present invention relates to the use of glutamic acid analogs and gamma-aminobutyric acid (GABA) for the treatment of insomnia.
PRIOR ART The GABA analogs used are known agents useful in anticonvulsant therapy for diseases of the central nervous system such as epilepsy, Huntington's chorea, cerebral ischemia, Parkinson's disease, tardive dyskinesia and spasity. It has also been suggested that the compounds can be used as antidepressants, anxiolytics and antipsychotics. See WO 92/09560 (Serial No. 618,692 filed November 27, 1990) and WP 93/23383 (Serial number of the United States 886,080 filed May 20, 1992).
The publication WO 97/33858 teaches that the compounds related to gabapentin are useful or treat epilepsy, mental lacunae, hypokinesia, cranial diseases, neurodegenerative diseases, depression, anxiety, panic, pain and diseases. neuropathological The WO publication
97/33858 does not specify what forms of pain are treated.
Additionally, the compounds of the invention are known for the treatment of neuropathic pain. For example, see Rosner H; Rubin L; Kestenbaum A., Gapapentin adjunctlve therapy in neurophatic paln states. Clin J Pain, 1996 Mar, 12: 1, 56-8; Segal AZ; Rordorf G., Gabapentin as a novel treatment for postherpetic neuralgia. Neurology, 1996 Apr, 46: 4, 1175-6; Wetzel CH; Connelly JF., Use of gabapentin in pain management. Ann Pharmacother, 1997 Sep, 31: 9, 1082-3; Zapp JJ., Postpoliomyelitis pain treated with gabapentin [letter]. Am Fam Physician, 1996 Jun, 53.8, 2442, 2445; Cheville A, et al., Neuropathic pain in radiation myelopathy: a case report. Program book, American Pain Society (14th Annual Scientific Meeting). Abstract # 95823, p. A-115; Sist T; Filadora V; Miner M; Lemma M., Gabapentin for idiopathic trigeminal neuralgia: report of two cases. Neurology, 1997 May, 48: 5, 1467; Waldman SD, Tutorial 28: Evaluation and Treatment of Trigeminal Neuralgia. Pain Digest (1997) 7: 21-24; Mellick LB; Mellick GA., Successful treatment of reflex sympathetic dystrophy with gabapentin [letter]. Am J Emerg Med, 1995 Jan, 13: 1, 96; Mellick GA; Seng MI., The use of gabapentin in the treatment of sympathetic reflex dystrophy and a phobic disorder. Am J Pain Manage 1995; 5: 7-9; Mellick GA; Mellicy LB; Mellick LB., Gabapentin in the management of reflex sympathetic dystrophy [letter]. J. Symptom Manage, 1995 May, 10: 4, 265-6; Mellick GA; Mellick LB., Reflex sympathetic dystrophy treated with gabapentin. Arch Phys Med Rehabil, 1997 Jan, 78: 1, 98-105 and Mackin GA., Medical and pharmacologic management of upper limb neuropathic pain syndromes. J Hand Ther, 1997 Apr-Jun, 10: 2, 96-109.
Insomnia and sleeplessness are common problems. Usually, insomnia or sleeplessness is precipitated by stress, emotional and physical causes.
The Patent of E.U.A. No. 5,510,381 directed to the use of gabapentin to treat manias, mentions a study in which it has been found that gabapentin improves delta wave (deep) sleep. This effect is beneficial in acute mania and also leads to the reduction of the risk of the beginning of a new episode of mania.
SUMMARY OF THE INVENTION This invention provides a method for the treatment of insomnia that, with a mammal comprising administration to a subject suffering from insomnia, an effective amount of a GABA analogue. A preferred embodiment uses a cyclic amino acid compound of Formula I
wherein R- is hydrogen or lower alkyl and n is an integer from 4 to 6 and pharmaceutically acceptable salts thereof. An especially preferred embodiment uses a compound of Formula I wherein R-i is hydrogen and n is 4, which compound is 1- (aminomethyl) -cyclohexane acetic acid, known generically as gabapentin.
In another embodiment, the invention includes the treatment of insomnia with a compound of Formula II
II wherein R2 is a long or branched chain alkyl of 1 to 6 carbon atoms, phenyl or cycloalkyl having from 3 to 6 carbon atoms; R3 is hydrogen or methyl and R4 is hydrogen, methyl or carboxyl or a single enantiomeric isomer or a pharmaceutically acceptable sai thereof, in unit dosage form, to a mammal in need of such treatment.
Preferred compounds of the invention are those wherein R and R3 are hydrogen and R2 is - (CH2) 0.2-i C4H9 as an (R), (S) or (R, S) isomer.
The most preferred compounds of the Formula II of the invention are (S) -3- (amomethyl) -5-methylhexanoic acid and 3-aminomethyl-5-methyl-hexanoic acid, known generically as pregabalin.
DETAILED DESCRIPTION OF THE PREFERRED MODALITIES The method of this invention uses any GABA analog. A GABA analog is any compound derived from or based on gamma-aminobutyric acid. The compounds are readily available either commercially or by synthetic methodology well known to those skilled in the art of organic chemistry. The preferred GABA analogs to be used in the method of this invention are cyclic amino acids of Formula I. These are described in U.S. Patent No. 4,024,175, which is incorporated herein by reference. Another preferred method uses the GABA analogs of Formula II and these are described in the U.S. Patent. 5,563,175 which is incorporated herein by reference.
All that is required to practice the method of this invention is to administer a GABA analog in an amount that is effective in treating insomnia. Said amounts will generally be from about 1 to about 300 mg per kg of the subject's body weight. Typical doses will be from about 10 to about 5000 mg per day for an adult of normal weight. It is expected that the common doses that should be administered could be from 100 mg three times a day up to 600 mg four times a day. Commercially available capsules of 100 mg, 300 mg and 400 mg of gabapentin can be administered. Alternative forms include liquids and tablets with an enteric layer.
If a compound of Formula II, such as pregabalin is used, the dose level is one sixth of gabapentin. The dose range for gabapentin is from about 0.15 mg to about 50 mg per kg per day of the subject's body weight. Typical doses for gabapentin will be from about 1.6 mg to about 840 mg per day with individual doses ranging from about 0.15 mg to about 65 mg per dose.
The compounds used in the present invention can form pharmaceutically acceptable salts with both inorganic and organic acids or bases. For example, the acid addition salts of the basic compounds are prepared by dissolving the free base in aqueous alcohol solution or aqueous solution or other suitable solvents containing the appropriate acid and isolating the salt by evaporating the solution . Examples of pharmaceutically acceptable salts are hydrochlorides, hydrobromides, hydrosulphates, etc., as well as sodium, potassium and magnesium salts, etc.
The compounds of Formula II may contain one or more asymmetric carbon atoms. The invention includes the individual enantiomers or diastomers and mixtures thereof. Enantiomers or diastomers can be prepared or isolated by methods well known in the art.
The pharmaceutical compositions of the compound of the present invention or its salts are produced by the formulation of the active compound in unit dosage form with a pharmaceutical carrier. Some examples of unit dosage forms are tablets, capsules, pills, powders, aqueous and non-aqueous oral solutions and suspensions and parenteral solutions packaged in containers containing one or more number of dose units and which are capable of being subdivided into individual doses. . Some examples of pharmaceutically suitable carriers, including pharmaceutical diluents are gelatin capsules; sugars such as lactose and sucrose; starches such as corn starch and potato starch, cellulose derivatives such as sodium carboxymethyl cellulose, ethyl cellulose, methyl cellulose and cellulose acetate phthalate; gelatin, talcum, stearic acid, magnesium stearate, vegetable oils such as peanut oil, cottonseed oil, sesame oil, olive oil, corn oil and theobroma oil; propylene glycol, glycerin, sorbitol, polyethylene glycol, water, agar gum, alginic acid, isotonic saline and phosphate stabilizer solutions, as well as other compatible substances normally used in pharmaceutical formulations. The compositions of the invention may also contain other components such as coloring agents, flavoring agents and / or preservatives. These materials, if present, are commonly used in relatively small quantities. The compositions may, if desired, also contain other therapeutic agents.
The percentage of the active ingredient in the preceding compositions may vary within wide limits, but for practical purposes is preferably present at a concentration of at least 10% in a solid composition and at least 2% in a primary liquid composition. The most satisfactory compositions are those in which a much higher proportion of the active compound is present.
The routes of administration of the subject compound or its salts are oral or parenteral. For example, a useful intravenous dose is between 5 and 50 mg and a useful oral dose is between 20 and 800 mg. The dose is within the range of doses used in the treatment of pain or according to the needs of the patient as they are described by the doctor.
The benefit of using GABA analogs to treat insomnia is that they do not cause addiction. Additionally, GABA analogues have a half-life in the body that is appropriate for working at night and subsequently cleansing the body in the morning to allow easy awakening. The GABA analogues, particularly gabapentin, the method of action is different from other sleep enhancement agents. GABA analogs can be combined with other agents to improve the sleep-inducing effects. Such agents include melatonin, tritofan, valerian, passionflower, antihistamines such as diphenhydramine hydrochloride or doxylamine succinate, densoquiacepene and non-benzo-dependent hypnotics.
Additional advantages of the use of the compounds of Formula I and I, especially gabapentin and pregabalin, in the present invention include the relatively non-toxic nature of the compounds, easy preparation, the fact that the compounds are well tolerated and the ease of the IV administration of drugs. Gabapentin has few interactions with the important classes of drugs that are not metabolized in the liver but are excreted unchanged. In addition, drugs are not metabolized in the body. The subjects treated with the method of the present invention are mammals including humans.
The GABA analogs used in the method of the present invention are not addictive.
This is a significant advantage over other sleep aids. These compounds also have a half-life that is appropriate for working at night and subsequently cleaning the body in the morning to allow easy awakening. The method of action of GABA analogs is different from other hypnotics and can therefore be combined with them to increase the inducing effects of sleep. These agents may include melatonin, tryptophan, valerian, passionflower, classical antihistamines such as defenidramin, hydrochloride or doxylamine succinate, as well as benzodiazepene and hypnotics, not benzodiazepene.
Claims (9)
1. A method for the treatment of a mammal suffering from insomnia comprising the administration to said mammal of a pharmaceutical composition comprising an effective amount of a GABA analogue.
2. The method according to claim 1, wherein the GABA analog is the compound according to Formula I: wherein Ri is hydrogen or lower alkyl and n is an integer of 4 to 6 carbon atoms and pharmaceutically acceptable salts thereof.
3. The method according to claim 2, wherein Formula I comprises gabapentin.
4. The method according to claim 2, comprising from about 10 mg to about 400 mg of Formula I.
5. The method according to claim 3, comprising from about 10 mg to about 400 mg of gabapentin.
6. The method according to claim 1, wherein the GABA analog is a compound according to Formula II: R-II wherein R2 is a long or branched chain alkyl of 1 to 6 carbon atoms, phenyl or cycloalkyl having from 3 to 6 carbon atoms; R3 is hydrogen or methyl and F is hydrogen, methyl or carboxyl.
7. The method according to claim 11, wherein Formula II comprises pregabalin.
8. The method according to claim 11, comprising from about 0.15 mg to about 65 mg of Formula II.
9. The method according to claim 12, comprising from about 0.15 mg to about 65 mg of pregabalin.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
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US60/092,166 | 1998-07-09 |
Publications (1)
Publication Number | Publication Date |
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MXPA00011509A true MXPA00011509A (en) | 2001-09-07 |
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