JP2009539921A - 神経精神障害の治療用の非不安誘発性精神賦活薬の製造のための1,7−ジメチルキサンチンの使用 - Google Patents
神経精神障害の治療用の非不安誘発性精神賦活薬の製造のための1,7−ジメチルキサンチンの使用 Download PDFInfo
- Publication number
- JP2009539921A JP2009539921A JP2009514766A JP2009514766A JP2009539921A JP 2009539921 A JP2009539921 A JP 2009539921A JP 2009514766 A JP2009514766 A JP 2009514766A JP 2009514766 A JP2009514766 A JP 2009514766A JP 2009539921 A JP2009539921 A JP 2009539921A
- Authority
- JP
- Japan
- Prior art keywords
- paraxanthine
- anxiety
- disorder
- treatment
- use according
- 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.)
- Pending
Links
Images
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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
- A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- 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
- A61P25/22—Anxiolytics
-
- 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
- A61P25/24—Antidepressants
-
- 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
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/34—Tobacco-abuse
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Neurology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Addiction (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Epidemiology (AREA)
- Hospice & Palliative Care (AREA)
- Anesthesiology (AREA)
- Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
試験は、試験時において体重25〜35gの雄CD1 albinoマウス(Charles River)を用いて実施した。これらの動物を20匹ずつプレキシガラスケージ(38×24×18cm)に入れ、温度を21±1℃に維持した換気式動物施設内で飼育した。これらの動物は水および食物を自由に得ることができ;人工照明で昼夜周期(昼間7:00a.m.〜7:00p.m.間)を確立した。試験は11:00a.m.〜6:00p.m.間に行った。
試験は、実施例1の場合と同じ系統のマウスで実施し、同じ条件下で維持した。
試験は、実施例1の場合と同じ系統のマウスで実施し、同じ条件下で維持した。
試験は、実施例1の場合と同じ系統のマウスで実施し、同じ条件下で維持した。
試験は、Vogel et al.(Psychopharmacologia, 1971, 21: 1-7)によって記載されている手順に従って、体重180g〜280gの雄Wistarラットを用いて実施した。動物を48時間絶水させた後、フロアが1cm間隔の導電性金属棒からなるプレキシガラスチャンバー(15×32×34cm)に個別に入れた。チャンバーの壁の1つの中央に電気ショック発生器(1.7mA;1秒)に接続された金属カップを置いた。
試験は、Aron et al. (Neuropharmacology, 1971, 10:459-469)によって記載されている方法に従って、体重20g〜30gのNMRIマウスを用いて実施した。動物を、フロアが電気ショック発生器(2.5mA;1.5秒)に独立に接続された4枚の金属プレートからなるプラスチックチャンバーに入れた。動物は、最初15秒間自由に装置を探索できる状態にし、その後、動物が2枚の金属プレート間を横断するたびに動物に電気ショックを与えた。横断数の増加は抗不安活性を示し、一方、この数の減少は不安惹起活性を示す。
・American Psychiatric Association (1987) Diagnostic and statistical manual of mental disorders. Washington, D. C: American Psychiatric Association.
・ American Psychiatric Association (1994) Diagnostic and statistical manual of mental disorders - Fourth Edition (DSM-IV) .
・Bernstein GA, Carroll ME, Crosby RD, Perwien AR, Go FS, Benowitz NL (1994) Caffeine effects on learning, performance, and anxiety in normal school-age children. J Am Acad Child Adolesc Psychiatry 33: 407-415.
・Boulenger JP, Uhde TW, Wolff EA, III, Post RM (1984) Increased sensitivity to caffeine in patients with panic disorders. Preliminary evidence. Arch Gen Psychiatry 41: 1067-1071.
・Greden JF (1974) Anxiety or caffeinism: a diagnostic dilemma. Am J Psychiatry 131: 1089-1092.
・Jiang M, Kameda K, Han LK, Kimura Y, Okuda H (1998) Isolation of lipolytic substances caffeine and 1,7- dimethylxanthine from the stem and rhizome of Sinomenium actum. Planta Med 64: 375-377.
・Muller CE, Shi D, Manning MJr, Daly JW (1993) Synthesis of paraxanthine analogs (1, 7-disubstituted Xanthines) and other xanthines unsubstituted at the 3-position: structure-activity relationships at adenosine receptors. J Med Chem 36: 3341-3349.
・Nickell PV, Uhde TW (1994) Dose-response effects of intravenous caffeine in normal volunteers. Anxiety 1: 161-168.
・Schmidt P, Eichenberger K, Druey J (1958) 1-Pyrazolo [3, 4- d] pyrimidines with caffeine-like structure and activity. HeIv Chim Acta 41: 1052-1060.
・Stern KN, Chait LD, Johanson CE (1989) Reinforcing and subjective effects of caffeine in normal human volunteers. Psychopharmacology (Berl) 98: 81-88.
・Yesair DW, Branfman AR, Callahan MM (1984) Human disposition and some biochemical aspects of methylxanthines. Prog Clin Biol Res 158: 215-233.
Claims (10)
- 神経精神障害の治療用の非不安誘発性精神賦活薬剤の製造のための、パラキサンチンの使用。
- 前記神経精神障害が疲労、睡眠障害または注意障害である、請求項1に記載の使用。
- 前記神経精神障害が不安障害である、請求項1に記載の使用。
- 前記神経精神障害が認知障害である、請求項1に記載の使用。
- 前記睡眠障害または注意障害が、特発性過眠症またはナルコレプシーである、請求項2に記載の使用。
- 前記薬剤が、鬱病、線維筋痛症、過敏性腸症候群、ニコチン離脱、パーキンソン病、多発性硬化症、筋萎縮性側索硬化症、時差ぼけまたは交代勤務による影響を受ける患者の疲労、睡眠障害または注意障害の治療用の薬剤である、請求項2に記載の使用。
- 前記薬剤が、鬱病またはニコチン離脱による影響を受ける患者の不安障害の治療用の薬剤である、請求項3に記載の使用。
- 前記薬剤が、注意欠陥/多動性障害の治療用の薬剤である、請求項1に記載の使用。
- 前記薬剤が、統合失調症に罹患している患者の認知障害の治療用の薬剤である、請求項4に記載の使用。
- 前記認知障害が、加齢またはアルツハイマー病に関連するものである、請求項4に記載の使用。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR0605189A FR2902010B1 (fr) | 2006-06-12 | 2006-06-12 | Utilisation de la 1,7 dimethylxanthine pour la fabrication d'un medicament psychoanaleptique non anxiogene destine au traitement d'un trouble neuropsychiatrique |
PCT/EP2007/055668 WO2007144315A1 (en) | 2006-06-12 | 2007-06-08 | Use of 1,7-dimethylxanthine for the manufacture of a non-anxiogenic psychoanaleptic drug for the treatment of a neuropsychiatric disorder |
Publications (1)
Publication Number | Publication Date |
---|---|
JP2009539921A true JP2009539921A (ja) | 2009-11-19 |
Family
ID=37592447
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2009514766A Pending JP2009539921A (ja) | 2006-06-12 | 2007-06-08 | 神経精神障害の治療用の非不安誘発性精神賦活薬の製造のための1,7−ジメチルキサンチンの使用 |
Country Status (8)
Country | Link |
---|---|
US (1) | US20090325984A1 (ja) |
EP (1) | EP2026812A1 (ja) |
JP (1) | JP2009539921A (ja) |
AR (1) | AR061446A1 (ja) |
CA (1) | CA2654891A1 (ja) |
FR (1) | FR2902010B1 (ja) |
TW (1) | TW200815013A (ja) |
WO (1) | WO2007144315A1 (ja) |
Families Citing this family (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2014065446A1 (ko) * | 2012-10-24 | 2014-05-01 | (주)라이프앤진 | 카페인과 파라잔틴에 의한 지방 분해 슬리밍 조성물 |
US11950616B2 (en) | 2019-06-21 | 2024-04-09 | Axcess Global Sciences, Llc | Non-vasoconstricting energy-promoting compositions containing ketone bodies |
WO2021151094A1 (en) * | 2020-01-23 | 2021-07-29 | Ingenious Ingredients, LP | Paraxanthine-based bioactive composition and method of use thereof |
TW202227085A (zh) * | 2020-09-14 | 2022-07-16 | 美商萊罕製藥股份有限公司 | 氘代副黃嘌呤(paraxanthine)及其用途 |
JP2024511169A (ja) * | 2021-03-26 | 2024-03-12 | ピーエックス・アイエヌジー,エルエルシー | 運動誘発性精神疲労を低減するためのパラキサンチンの使用 |
EP4313056A1 (en) * | 2021-03-31 | 2024-02-07 | Px Ing, Llc | The use of paraxanthine to improve performance in video gamers |
WO2022232469A1 (en) | 2021-04-29 | 2022-11-03 | Revel Technologies, Inc. | Compositions and methods for their production |
WO2023009681A1 (en) * | 2021-07-27 | 2023-02-02 | Ingenious Ingredients, LP | Paraxanthine-based caffeine substitute compositions and method of use thereof in slow caffeine metabolizers |
US20230113817A1 (en) * | 2021-10-12 | 2023-04-13 | Ingenious Ingredients, LP | Dileucine compositions and methods of use thereof for fat loss |
US20230165868A1 (en) * | 2021-11-28 | 2023-06-01 | Ingenious Ingredients, LP | Paraxanthine-based compositions for enhancing muscle function, nitric oxide signaling, and/or muscle glycogen levels |
US11969430B1 (en) * | 2023-03-10 | 2024-04-30 | Axcess Global Sciences, Llc | Compositions containing paraxanthine and beta-hydroxybutyrate or precursor for increasing neurological and physiological performance |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2001080893A1 (fr) * | 2000-04-26 | 2001-11-01 | Eisai Co., Ltd. | Compositions medicinales favorisant les mouvements intestinaux |
WO2004076675A2 (en) * | 2003-02-26 | 2004-09-10 | Johns Hopkins University | Glutamate transport modulatory compounds and methods |
JP2009528059A (ja) * | 2006-02-28 | 2009-08-06 | メタボロン インコーポレイテッド | 筋萎縮性側索硬化症に関するバイオマーカー及びそれらを使用する方法 |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1998766A2 (en) * | 2005-12-16 | 2008-12-10 | Ironwood Pharmaceuticals, Inc. | Useful indole compounds |
-
2006
- 2006-06-12 FR FR0605189A patent/FR2902010B1/fr not_active Expired - Fee Related
-
2007
- 2007-06-07 TW TW096120502A patent/TW200815013A/zh unknown
- 2007-06-08 CA CA002654891A patent/CA2654891A1/en not_active Abandoned
- 2007-06-08 EP EP07730023A patent/EP2026812A1/en not_active Withdrawn
- 2007-06-08 WO PCT/EP2007/055668 patent/WO2007144315A1/en active Application Filing
- 2007-06-08 JP JP2009514766A patent/JP2009539921A/ja active Pending
- 2007-06-08 US US12/304,377 patent/US20090325984A1/en not_active Abandoned
- 2007-06-12 AR ARP070102566A patent/AR061446A1/es not_active Application Discontinuation
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2001080893A1 (fr) * | 2000-04-26 | 2001-11-01 | Eisai Co., Ltd. | Compositions medicinales favorisant les mouvements intestinaux |
WO2004076675A2 (en) * | 2003-02-26 | 2004-09-10 | Johns Hopkins University | Glutamate transport modulatory compounds and methods |
JP2009528059A (ja) * | 2006-02-28 | 2009-08-06 | メタボロン インコーポレイテッド | 筋萎縮性側索硬化症に関するバイオマーカー及びそれらを使用する方法 |
Non-Patent Citations (3)
Title |
---|
JPN5009007719; SCHWARZSCHILD M.A. et al.: NEUROLOGY Vol. 61, No. Suppl 6, 200312, p. S55-S61 * |
JPN5009007721; Xu, K. et al.: 'NEUROPROTECTION BY METABOLITES OF CAFFEINE MAY PROLONG ITS NEUROPROCTECTIVE EFFECT IN THE MPTP MODEL' Society for Neuroscience Abstract Viewer and Itinerary Planner Vol. 2002, 2002, pp. Abstract No. 487.5 * |
JPN6012045667; Logan, Lance et al.: Pharmacology, Biochemistry and Behavior Vol. 24, No. 5, 1986, p. 1281-1286 * |
Also Published As
Publication number | Publication date |
---|---|
FR2902010A1 (fr) | 2007-12-14 |
US20090325984A1 (en) | 2009-12-31 |
FR2902010B1 (fr) | 2008-08-22 |
EP2026812A1 (en) | 2009-02-25 |
TW200815013A (en) | 2008-04-01 |
CA2654891A1 (en) | 2007-12-21 |
AR061446A1 (es) | 2008-08-27 |
WO2007144315A1 (en) | 2007-12-21 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP2009539921A (ja) | 神経精神障害の治療用の非不安誘発性精神賦活薬の製造のための1,7−ジメチルキサンチンの使用 | |
Cunha et al. | Chronic caffeine consumption prevents memory disturbance in different animal models of memory decline | |
ES2344313T3 (es) | Composiciones farmaceuticas de un esteroide neuroactivo y usos de las mismas. | |
ES2675544T3 (es) | Tratamiento para trastornos mentales y neurológicos | |
Devan et al. | Phosphodiesterase inhibition by sildenafil citrate attenuates the learning impairment induced by blockade of cholinergic muscarinic receptors in rats | |
CN108420819A (zh) | 用于治疗神经障碍的新组合物 | |
CA2784132C (en) | Composition for improving brain function and method for improving brain function | |
JP6228212B2 (ja) | 記憶能力を改善するための向知性組成物 | |
TW202027751A (zh) | 慢性咳嗽治療用醫藥 | |
Verhey et al. | Olanzapine versus haloperidol in the treatment of agitation in elderly patients with dementia: results of a randomized controlled double-blind trial | |
MXPA05013148A (es) | Un metodo de tratamiento de un trastorno de la ansiedad. | |
US20090082341A1 (en) | 4-hydroxy-4-methyl-piperidine-1-carboxylic acid (4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide FOR THE TREATMENT OF POST-TRAUMATIC STRESS DISORDER | |
SHRIVASTAVA et al. | Epileptogenic Drugs and Seizures: A Comprehensive Review of Current Knowledge. | |
Patocka et al. | Coffee, caffeine and cognition: a benefit or disadvantage? | |
US20180055827A1 (en) | Treatment of autism and autism spectrum disorders (asd) | |
Vinogradova et al. | The effects of intranasal administration of oxytocin on the behavior of rats with different behavioral strategies subjected to chronic mild stress | |
AU2018227291B2 (en) | Method for preventing or treating autism spectrum disorders by benzoic acid salt | |
EP2617430A1 (en) | Composition for improving brain function and method for improving brain function | |
EP3714888A1 (en) | Compounds for use in the treatment of adcy5-related dyskinesia | |
EP2338503A1 (en) | Composition for improving brain function and method for improving brain function | |
Stein et al. | Inattention and hyperactivity-impulsivity: psychobiological and evolutionary underpinnings of ADHD | |
Santiago | Evaluation of Seizure Threshold as an Early Behavioral Marker of Disease Progression in the Mouse Model of Mucopolysaccharidosis IIIA | |
JP5479884B2 (ja) | 脳機能改善用組成物および脳機能を改善する方法 | |
Harris et al. | O-104 Two Year Outcomes Of Children Treated With Dextrose Gel For Neonatal Hypoglycaemia: Follow Up Of A Randomised Trial | |
Laprairie et al. | Alterations in expression and function of phosphodiesterases in Huntington’s disease |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20100601 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20120831 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20121128 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20121205 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20121228 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20130110 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20130130 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20130206 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20130507 |