WO2006085688A1 - Agent thérapeutique contre la douleur psychogène - Google Patents

Agent thérapeutique contre la douleur psychogène Download PDF

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Publication number
WO2006085688A1
WO2006085688A1 PCT/JP2006/302788 JP2006302788W WO2006085688A1 WO 2006085688 A1 WO2006085688 A1 WO 2006085688A1 JP 2006302788 W JP2006302788 W JP 2006302788W WO 2006085688 A1 WO2006085688 A1 WO 2006085688A1
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pain
neuropathic pain
therapeutic agent
inhibitor
phenylethanolamine
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PCT/JP2006/302788
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English (en)
Japanese (ja)
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Tsutomu Tanabe
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Japan Science And Technology Agency
Tokyo Medical And Dental University
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Priority to JP2007502684A priority Critical patent/JPWO2006085688A1/ja
Publication of WO2006085688A1 publication Critical patent/WO2006085688A1/fr

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    • 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
    • A61K31/13—Amines
    • A61K31/133—Amines having hydroxy groups, e.g. sphingosine
    • 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
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
    • 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
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/472—Non-condensed isoquinolines, e.g. papaverine
    • 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
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • 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
    • 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
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A61P29/02—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] without antiinflammatory effect
    • 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
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P41/00—Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/12—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
    • C07D217/14—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring other than aralkyl radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
    • C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D223/16—Benzazepines; Hydrogenated benzazepines

Definitions

  • the present invention relates to a therapeutic agent for neuropathic pain having an excellent pain suppressing effect on neuropathic pain, a method for treating neuropathic pain using such a therapeutic agent, and the like.
  • Neuropathic pain is pain caused by damage or dysfunction of the peripheral nervous system or central nervous system, and is refractory pain that does not sufficiently respond to opioid drugs such as morphine.
  • opioid drugs such as morphine.
  • diseases associated with neuropathic pain include post-herpetic neuralgia, trigeminal neuralgia, diabetic neuralgia, and post-traumatic or post-traumatic prolonged pain. Can do.
  • central opioid analgesics such as morphine, and non-steroidal anti-inflammatory drugs (NSAIDS) such as indomethacin.
  • NSAIDS non-steroidal anti-inflammatory drugs
  • these analgesics are generally less effective against neuropathic pain, and analgesics that are effective against normal nociceptive pain (especially narcotic analgesics) may be less effective.
  • Inadequate analgesic effect of narcotic analgesics on neuropathic pain is a major feature of neuropathic pain. In some cases, neuropathic pain is diagnosed using this feature.
  • neuropathic pain has been treated by nerve block, neurosurgical treatment such as spinal epidural electrostimulation, tricyclic antidepressants, and intrathecal administration of drugs such as baclofun Etc. are known.
  • neurosurgical treatment such as spinal epidural electrostimulation, tricyclic antidepressants, and intrathecal administration of drugs such as baclofun Etc.
  • these treatments have problems that are not effective enough or have side effects.
  • capsaicin cream is effective for postherpetic neuralgia and pain syndrome after mastectomy by depleting pain substance substance P released from nerve terminals and reducing pain.
  • problems with burning pain caused by kabusaicin There are problems in terms of usability and safety.
  • neuropathic pain is an intractable disease, and no effective treatment has yet been established.
  • Histamine has a function as a neurotransmitter and neuromodulator and has been shown to work in the central nervous system and peripheral nervous system, and is involved in the regulation of blood pressure and pain.
  • serotonin nervous system is formed in the gastrointestinal tract and surrounding intestinal nervous system.
  • a system has been found and the serotonin nervous system of the brain acts as a neurotransmitter related to mood, sleep, appetite, body temperature, pain, blood pressure and vomiting.
  • catecholamines produced by the tyrosine-> dopa-> dopamine-> norepynephrine-> epinephrine pathway also play various roles in physiological responses.
  • Dopamine is a precursor of norepinephrine, but its action as a neurotransmitter dilates the blood vessels of the kidneys, relaxes the intestinal smooth muscle, and also affects blood pressure via the epinephrine receptor. ing. Epinephrine is related to metabolic systems such as blood pressure, smooth muscle, and pancreas. Norepinephrine is also called an alarm system in the brain, and when it becomes abnormal, various stress-related disorders occur.
  • these physiologically active amines express physiological actions via various receptor subtypes, for example, drugs (agonists) that specifically act on a certain receptor subtype, these amines Drugs that specifically antagonize the action of drugs (antagonists) or drugs that block the action (blockers) were expected to have an effect on neuropathic pain.
  • antidepressants are already used as analgesic aids mainly in the treatment of chronic pain.
  • most of the first and second generation tricyclic and tetracyclic antidepressants have inhibitory effects on the reuptake of both serotonin and norepinephrine.
  • it is non-selective and has many side effects such as anti-cholinergic rhinorrhea, constipation, dysuria, dullness due to anti-histamine, or anti-adrenergic ⁇ -orthostatic hypotension. It has been found.
  • SSRI selective serotonin reuptake inhibitor
  • SSRI selective serotonin reuptake inhibitor
  • SSRI selective serotonin reuptake inhibitor
  • Psychiatric symptoms such as nausea, rhinorrhea, constipation, hallucinations, delusions, sometimes hypersensitivity, hematopoietic disorder, liver disorder, and combined use with other antipsychotic drugs, strong muscle rigidity, difficulty swallowing, tachycardia
  • serotonin syndrome due to abnormally increased serotonin activity in the brain, such as ventricular arrhythmia and other cardiovascular side effects when combined with fever or tranquilizers.
  • the fourth-generation SNRI (the serotonin and norepinephrine reuptake inhibitor), which is said to have the least side effects, generally has drowsiness, nausea, phlegm, constipation, etc., heart, kidney, liver People with disabilities have the side effects of being prone to convulsions, leukopenia, and glaucoma. As with SSRIs, there are many interactions with concomitant drugs, so handling with great care is necessary.
  • Japanese National Publication No. 9-511739 and Japanese National Publication No. 2002-537245 disclose serotonin (5-- ⁇ 3) receptor for non-inflammatory local diseases such as fibromyalgia (fibromyalgia).
  • body antagonists is described.
  • Japanese Patent Publication No. 2002-523366 describes the use of dopamine reuptake inhibitors for various functional disorders including pain.
  • JP 2000-507544 A discloses a combination of an atypical antipsychotic drug (clozapine, risperidone, taetiapine, perospirone, olanzapine, etc.) and a drug used for pain.
  • JP-T-2002-503224 describes serotonin reuptake inhibitors, combined serotonin mononorpinephrine reuptake inhibitors, serotonin receptor agonists and antagonists as synergistic analgesics.
  • phenylethanolamine N_methyltransferase is an enzyme that catalyzes the biosynthesis of epinephrine from norepinephrine, which is the final step in the catecholaminergic system, and is also important for blood pressure regulation and neuroendocrine function Plays an important role.
  • an object of the present invention is to provide a novel therapeutic agent for neuropathic pain that exhibits an excellent effect on intractable pain called neuropathic pain.
  • the present inventors have conducted research based on an original idea to achieve the above-mentioned problem.
  • a B (phenylethanolamine ⁇ -methyltransferase) inhibitor typified by DCMB is present. It was found that it exhibits a high analgesic effect, and the present invention was completed.
  • the present invention provides the following therapeutic agent for neuropathic pain, a pharmaceutical composition for treating neuropathic pain, a method for treating neuropathic pain, and the like.
  • Phenylethanolamine ⁇ -methyltransferase A therapeutic agent for neuropathic pain containing an inhibitor as an active ingredient.
  • the therapeutic agent for neuropathic pain according to the above (1) which is selected from pharmaceutically acceptable salts thereof.
  • PNMT inhibitor is selected from (Sat) 1,2,3-Dichloro mouth ⁇ -methylbenzylamine (D CMB) and pharmaceutically acceptable salts thereof
  • Neuropathic pain includes postherpetic neuralgia, trigeminal neuralgia, diabetic neuralgia, cancer pain, postoperative or posttraumatic prolonged pain, hyperalgesia, alodynia, postthoracotomy pain, CRP
  • neuropathic pain in multiple sclerosis, AI DS, thalamic pain, paraplegia due to spinal cord disorder, non-sensory pain and phantom limb pain
  • AI DS thalamic pain
  • paraplegia due to spinal cord disorder
  • non-sensory pain non-sensory pain
  • phantom limb pain The therapeutic agent for neuropathic pain according to any one of (3) to (3).
  • a pharmaceutical composition for treating neuropathic pain comprising a phenylethanolamine N-methyltransferase (PNMT) inhibitor and a pharmaceutically acceptable carrier.
  • PNMT phenylethanolamine N-methyltransferase
  • PNMT phenylethanolamine N-methyltransferase
  • PNMT phenylethanolamine N-methyltransferase
  • FIG. 1 is a diagram showing the experimental results of Example 1, in which DCM B was intraperitoneally administered to hypersensitivity rats and the change in pain threshold with respect to mechanical stimulation was shown.
  • FIG. 2 is a diagram showing the experimental results of Example 2, in which DCM B was intraperitoneally administered to hypersensitivity rats and the change in the pain threshold with respect to thermal stimulation was shown.
  • the present invention relates to a neuropathic pain therapeutic agent comprising a PNMT (phenylethanolamine N-methyltransferase) inhibitor as an active ingredient, a neurogenic pain comprising a PNMT inhibitor and a pharmaceutically acceptable carrier.
  • PNMT phenylethanolamine N-methyltransferase
  • D CM B ((Sat) _ 2,3-Dichloro-1- ⁇ -methylbenzylamine) is well known, but surprisingly, the present inventor We found for the first time that the inhibitor D CMB alone has a therapeutic effect on neuropathic pain.
  • phenylethanolamine N-methyltransferase (P NMT) inhibitor inhibits the action of an enzyme that catalyzes the biosynthesis of ebinephrine from norepinephrine, which is the final step in the catecholaminergic system. Means a compound.
  • Epinephrine biosynthesis inhibitory action is a known method, for example, This can be confirmed by the method described in Endocrinology Vol. 141, No. 3 1142-1150 (2000).
  • the term “treatment” generally refers to amelioration of symptoms in humans and non-human mammals.
  • the term “improvement” refers to, for example, the case where the degree of the disease is reduced or not worsened compared to the case where the therapeutic agent of the present invention is not administered, and also includes the meaning of prevention.
  • pharmaceutical composition means a composition containing an active ingredient (DCMB, etc.) useful in the present invention and an additive such as a carrier used in the preparation of a medicament.
  • PNMT phenylethanolamine N-methyltransferase inhibitor
  • PNMT inhibitor described above are known, Merck Index (The Merck Index, 13 th Edition (2001), various documents, pharmacology reference books (e.g., The pharmacological basis of therapeutics 9 th Edition, the Mcuraw Hill), etc.
  • DCMB is commercially available and can be obtained from, for example, Sigma-A 1 drich, and DCMB is available on the company's website. Physicochemical properties and related main literature can be confirmed.
  • containing a phenylethanolamine N-methyltransferase (P NMT) inhibitor as an active ingredient refers to a compound known as a P NMT inhibitor and a compound of this compound. It is intended to encompass all uses in pharmaceutically acceptable forms (eg, its salts, esters, amides, hydrated or solvated forms, racemic mixtures, optically pure forms, oral drugs, etc.). Used.
  • the compound as an active ingredient used in the present invention may be a free form or a pharmaceutically acceptable salt.
  • Such “salts” include acid salts and base salts.
  • acid salts include hydrochloride, hydrobromide, hydroiodide, nitrate, sulfate, bisulfate, phosphate, acid phosphate, acetate, lactate, and citrate.
  • Salt acid citrate, tartrate, bitartrate, succinate, maleate, fumarate, dalconate, saccharide, benzoate, methanesulfonate, ethanesulfonate, benzenesulfone Acid salt, p-toluenesulfonate, 1,1'-methylene monobis mono (2-hydroxy mono 3-naphthoic acid) salt, and the like.
  • the base salt include alkali metal salts such as sodium salt and potassium salt, alkaline earth metal salts such as strong salt and magnesium salt, water-soluble amine addition salts such as ammonium salt and N-methyl darcamamine salt, Examples include lower alcohol salts, salts derived from other bases of pharmaceutically acceptable organic amines.
  • the therapeutic agent and composition for neuropathic pain of the present invention are effective for the treatment of neuropathic pain.
  • neuropathic pain include, for example, postherpetic neuralgia, trigeminal neuralgia, diabetic neuralgia, cancer pain, postoperative or posttraumatic prolonged pain, hyperalgesia, alodynia, postthoracotomy pain , CRPS, pain due to multiple sclerosis, AIDS, thalamic pain, paraplegic pain due to spinal cord injury, non-sensory pain, neuropathic pain in phantom limb pain, etc.
  • fibromagia fibromyalgia
  • fibromyalgia which has much in common with postherpetic neuralgia in the pathology, can be expected to have therapeutic effects.
  • the administration form of the therapeutic agent for neuropathic pain of the present invention is not particularly limited, and can be administered orally or parenterally.
  • D CM B which is a P NMT inhibitor, which is an active ingredient of the therapeutic agent for neuropathic pain of the present invention, may be formulated alone, Can be provided in the form of a preparation by blending an acceptable carrier or a pharmaceutical additive.
  • D CMB which is the active ingredient of the present invention can be contained in the preparation in an amount of 0.1 to 99.9% by weight, for example.
  • Examples of pharmaceutically acceptable carriers or additives include excipients, disintegrants, disintegration aids, binders, lubricants, coating agents, dyes, diluents, solubilizers, solubilizers, etc. Tonicity agents, pH adjusting agents, stabilizers, etc. can be used.
  • preparations suitable for oral administration include powders, tablets, capsules, fine granules, granules, solutions or syrups.
  • various excipients such as microcrystalline cellulose, sodium citrate, calcium carbonate, dipotassium phosphate, dalysin are used in starch, preferably corn, starch or tapio
  • various disintegrants such as alginic acid and certain key acid double salts and granulating binders such as polyvinylpyrrolidone, sucrose, gelatin, gum arabic.
  • lubricants such as magnesium stearate, sodium laurinosulfate and talc are often very effective for tablet formation.
  • the same kind of solid composition can also be used by filling gelatin capsules.
  • Suitable materials in this context include latatose or lactose, as well as high molecular weight polyethylene dallicol. If you want an aqueous suspension and / or elixir for oral administration, use the active ingredient in combination with various sweeteners or flavors, colorants or dyes, and if necessary, use emulsifiers and / or suspending agents. It can be used with water, ethanol, propylene glycol, glycerin, etc., and diluents that combine them.
  • preparations suitable for parenteral administration include injections and suppositories.
  • the active ingredient of the present invention can be dissolved in either sesame oil or peanut oil, or a solution dissolved in an aqueous propylene glycol solution can be used.
  • the aqueous solution should be buffered as appropriate (preferably pH 8 or higher), and the liquid diluent must first be made isotonic.
  • Such aqueous solutions are suitable for intravenous injection and oily solutions are suitable for intra-articular, intramuscular and subcutaneous injection. All of these solutions can be readily prepared by standard pharmaceutical techniques well known to those skilled in the art to produce aseptic conditions.
  • the active ingredient of the present invention can be administered locally such as on the skin. It is. In this case, topical administration in the form of creams, jellies, pastes, ointments is desirable according to standard pharmaceutical practice.
  • the dose of the therapeutic agent for neuropathic pain of the present invention is not particularly limited, and is appropriately administered according to various conditions such as the type of pain, the age and symptoms of the patient, the administration route, the purpose of treatment, and the presence or absence of a concomitant drug. It is possible to select the amount.
  • the dose of the therapeutic agent for neuropathic pain of the present invention (as the amount of the active ingredient) is, for example, about 100 to 25000 mg, preferably 150 to 9000 mg per day for an adult (for example, 60 kg body weight).
  • the dosage when administered as an injection is, for example, about 100 to 5000 mg, preferably 180 to 1800 mg per day for an adult (for example, 60 kg body weight). These daily doses may be administered in two to four divided doses.
  • a pain hypersensitivity model prepared by completely ligating the L5 / L6 spinal nerve to a 6-week-old male rat (weight: 196.2 to 221.9 g) was used.
  • the mechanical ⁇ U intense test uses Dynamic Planter Aesthesiometer (37400, ugobazinole), and the thermal stimulation test uses plantar thermal stimulation device (planter test 7370, ugobazil) to measure the pain threshold of model animals.
  • the groups were divided into groups using the preclinical package Vers ion 5.0 (SAS Institute Japan) so that the pain threshold measured before administration on each experimental day was uniform.
  • For mechanical stimulation animals with a foot pain threshold of 8.0 g or more for model animals were excluded from the study, and for heat stimulation, animals with a model foot pain threshold of 10 seconds or more were excluded from the study.
  • test substance is intended to confirm the direct action on the spinal cord, but it has been confirmed that it passes through the brain barrier. It was administered intraperitoneally at a volume of 10 ml / kg using a syringe barrel and needle.
  • the maximum pain threshold after administration was 5.7 g in the control group administered with physiological saline, whereas (a) 0.3 mg / kg was administered in the group administered DCMB.
  • the maximum threshold after administration was 6.3g
  • DCMB administration significantly increased the pain threshold at 3 mg / kg and 30 mg / kg, confirming the analgesic effect in neuropathic pain.
  • the control group that received saline solution had a maximum pain threshold after administration.
  • the maximum threshold after administration was 7.9 seconds for 0.3 mg / kg administration
  • (b) 3rag / kg administration When the maximum threshold was 9.4 seconds and (c) 30 mg / kg was administered, the maximum threshold after administration was 11.4 seconds.
  • DCMB administration significantly increased the pain threshold at 10 mg / kg, confirming analgesic effects in neuropathic pain.
  • the therapeutic agent for neuropathic pain containing a PNMT inhibitor such as DCMB of the present invention has the effect of improving the symptoms of neuropathic pain caused by various causes. It can be used effectively for treatment.

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Abstract

La présente invention concerne un agent thérapeutique contre la douleur psychogène, une maladie réfractaire, dont l'effet thérapeutique est excellent. Plus spécifiquement, la présente invention concerne un agent thérapeutique contre la douleur psychogène qui comprend un inhibiteur de phényléthanolamine-N-méthyl transférase (PNMT) tel que la DCMB ((±)-2,3-dichloro-α-méthylbenzylamine) au titre de principe actif, une préparation pharmaceutique pour le traitement de la douleur psychogène comprenant ledit inhibiteur de PNMT au titre de principe actif, et une méthode de traitement de la douleur psychogène employant ledit inhibiteur de PNMT.
PCT/JP2006/302788 2005-02-10 2006-02-10 Agent thérapeutique contre la douleur psychogène WO2006085688A1 (fr)

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JP2005033896A JP4222614B2 (ja) 2005-02-10 2005-02-10 神経因性疼痛治療剤

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Cited By (1)

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JP2010533660A (ja) * 2007-07-16 2010-10-28 ヨハン ウォルフガング ゲーテ−ウニベルジテート フランクフルト アム マイン 慢性疼痛の治療又は予防のためのグラニュリン又はグラニュリン様化合物の使用
US9655947B2 (en) 2007-07-16 2017-05-23 Johann Wolfgang Goethe-Universitat Frankfurt Am Main Use of a granulin or a granulin-like compound for the therapy or prophylaxis of chronic pain

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