(19) TZZ ¥_T (11) EP 2 288 345 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: A61K 31/045 (2006.01) A61K 45/06 (2006.01) 10.06.2015 Bulletin 2015/24 A61P 25/00 (2006.01) (21) Application number: 09733496.5 (86) International application number: PCT/IE2009/000021 (22) Date of filing: 20.04.2009 (87) International publication number: WO 2009/128058 (22.10.2009 Gazette 2009/43) (54) PSYCHO-PHARMACEUTICALS PSYCHOPHARMAZEUTIKA PRODUITS PSYCHO-PHARMACEUTIQUES (84) Designated Contracting States: • SCHAFFARZICK R W ET AL: "The anticonvulsant AT BE BG CH CY CZ DE DK EE ES FI FR GB GR activity and toxicity of methylparafynol HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL (dormison) and some other alcohols." SCIENCE PT RO SE SI SK TR (NEW YORK,N.Y.) 12 DEC 1952,vol. 116, no. 3024, 12 December 1952 (1952-12-12), pages 663-665, (30) Priority: 18.04.2008 IE 20080298 XP002538385 ISSN: 0036-8075 • GUPTA B D ET AL: "Emotion as a determinant of (43) Date of publication of application: the effects of drugs and their combination on 02.03.2011 Bulletin 2011/09 different components of behaviour in rats" NEUROPHARMACOLOGY, PERGAMON PRESS, (73) Proprietor: University College Dublin OXFORD, GB, vol. 11, no. 1, 1 January 1972 National University Of Ireland, Dublin (1972-01-01), pages 31-38, XP025490183 ISSN: Dublin 4 (IE) 0028-3908 [retrieved on 1972-01-01] • MAY P R A ET AL: "Dormison, a new type of (72) Inventors: hypnotic: its therapeutic use in psychiatric • REGAN, Ciaran patients" AMERICAN JOURNAL OF Dublin 8 (IE) PSYCHIATRY, AMERICAN PSYCHIATRIC • CONBOY, Lisa ASSOCIATION, WASHINGTON, DC, US, vol. 109, Dublin 18 (IE) no. 12, 1 June 1953 (1953-06-01), pages 881-888, • GANNON, Shane XP009120553 ISSN: 0002-953X Clonbur • KENNEDY D G ET AL: "Methylpentynol (oblivon) County Galway (IE) in the treatment of epilepsy." SCIENCE (NEW YORK, N.Y.) 16 SEP 1955, vol. 122, no. 3168, 16 (74) Representative: MacLachlan & Donaldson September 1955 (1955-09-16), page 515, 2b Clonskeagh Square XP002538386 ISSN: 0036-8075 Clonskeagh Road • MARRIOTT A S ET AL: "Effects of centrally acting Dublin 14 (IE) drugs on exploratory behaviour in rats." BRITISH JOURNAL OF PHARMACOLOGY AND (56) References cited: CHEMOTHERAPY OCT 1965, vol. 25, no. 2, GB-A- 1 415 228 US-A- 4 201 725 October 1965 (1965-10), pages 432-441, US-A- 4 223 041 XP002538476 ISSN: 0366-0826 Note: Within nine months of the publication of the mention of the grant of the European patent in the European Patent Bulletin, any person may give notice to the European Patent Office of opposition to that patent, in accordance with the Implementing Regulations. Notice of opposition shall not be deemed to have been filed until the opposition fee has been paid. (Art. 99(1) European Patent Convention). EP 2 288 345 B1 Printed by Jouve, 75001 PARIS (FR) (Cont. next page) EP 2 288 345 B1 • GUPTA ET AL: "An examination of the effects of • LEHMANN A ET AL: "A study of the effect of stimulant and depressant drugs on escape/ psychotropic drugs on the processes of avoidance conditioning in strains of rats excitation and inhibition of the CNS by the selectively bred for emotionality/non- audiogenic crisis test in the rat" emotionality: Intertrial activity" 19690501, vol. 8, PSYCHOPHARMACOLOGY, SPRINGER no. 3, 1 May 1969 (1969-05-01), pages 227-234, VERLAG, BERLIN, DE, vol. 3, no. 5, 1 January XP022252590 1962 (1962-01-01), pages 331-343, XP009120399 • GILLHESPY R O: "Methylpentynol carbamate in ISSN: 0033-3158 the management of insomnia and parkinsonism" • MARLEY E ET AL: "Clinical aspects of BRITISH JOURNAL OF CLINICAL PRACTICE,, susceptibility to methylpentynol." JOURNAL OF vol. 12, no. 3, 1 March 1958 (1958-03-01), pages NEUROLOGY, NEUROSURGERY, AND 191-193, XP009120346 ISSN: 0007-0947 PSYCHIATRY MAY 1958, vol. 21, no. 2, May 1958 • HELD R: "Trial therapy with methylpentynol (1958-05), pages 129-140, XP002538387 ISSN: carbamate in ambulatory psychiatric treatment" 0022-3050 SEMAINE DES HOPITAUX DE PARIS, • DICKER S E ET AL: "The effect of methylpentynol EXPANSIONSCIENTIFIQUE FRANCAISE, PARIS, in man." BRITISH JOURNAL OF FR, vol. 32, no. 23, 14 April 1956 (1956-04-14), PHARMACOLOGY AND CHEMOTHERAPY DEC pages 1326-1333, XP009120390 ISSN: 0037-1777 1957, vol. 12, no. 4, December 1957 (1957-12), • BROUSSOLLE P ET AL: "Effects of pages 479-483, XP002538388 ISSN: 0366-0826 methylpentynol carbamate in a severe • J. J Hagan: "Predicting Drug Efficacy for psychosis. Therapeutic action and critical Cognitive Deficits in Schizophrenia", phenomena" JOURNALDE MEDECINE DE LYON, Schizophrenia Bulletin, vol. 31, no. 4, 15 SN, LYON, FR, vol. 41, no. 960, 1 January 1960 September 2005 (2005-09-15), pages 830-853, (1960-01-01), pages 123-127, XP009120391 ISSN: XP055063328, ISSN: 0586-7614, DOI: 1157-0385 10.1093/schbul/sbi058 • HOUSER M ET AL: "Utilization of methylpentynol • Philippe Pichat ET AL: "SSR180711, a Novel carbamate in large doses in psychiatry" Selective [alpha]7 Nicotinic Receptor Partial JOURNAL DE MEDECINE DE LYON,, vol. 38, no. Agonist: (II) Efficacy in Experimental Models 918, 1 January 1958 (1958-01-01), pages 309-317, Predictive of Activity Against Cognitive XP009120547 Symptoms of Schizophrenia", • CIRILLI M ET AL: "On the association of Neuropsychopharmacology, vol. 32, no. 1, 1 psychotonic drugs and C.M.P. (methylparafynol January 2007 (2007-01-01), pages 17-34, carbamate) in psychiatric therapy" ANNALES XP055063326, ISSN: 0893-133X, DOI: MEDICO-PSYCHOLOGIQUES, FORTIN, PARIS, 10.1038/sj.npp.1301188 FR, vol. 119, no. 1, 1 February 1961 (1961-02-01), pages 285-299, XP009120395 ISSN: 0003-4487 • LECOQ R ET AL: "The course of alcoholic desintoxication and its application in some types of serious encephalopathies" ENCEPHALE, PARIS, FR, vol. 53, no. 1, 1 January 1964 (1964-01-01), pages 35-61, XP009120397 ISSN: 0013-7006 2 EP 2 288 345 B1 Description TECHNICAL FIELD 5 [0001] The present invention relates to novel therapeutic uses of Meparfynol and its pharmaceutically acceptable salts. In particular, the present invention concerns the use of Methyl Pentynol (also known as Meparfynol) or a pharma- ceutically acceptable salt thereof for the treatment and/or prevention of schizophrenia. BACKGROUND OF THE INVENTION 10 [0002] Psychosis is a symptom of severe mental illness. Although it is not exclusively linked to any particular psycho- logical or physical state, it is particularly associated with schizophrenia, bipolar disorder (manic depression) and severe clinical depression. Psychosis is characterized by disorders in basic perceptual, cognitive, affective and judgmental processes. Individuals experiencing a psychotic episode may experience hallucinations (often auditory or visual hallu- 15 cinations), hold paranoid or delusional beliefs, experience personality changes and exhibit disorganised thinking (thought disorder). This is sometimes accompanied by features such as a lack of insight into the unusual or bizarre nature of their behaviour, difficulties with social interaction and impairments in carrying out the activities of daily living. [0003] Psychosis is not uncommon in cases of brain injury and may occur after drug use, particularly after drug overdose or chronic use. Certain compounds may be more likely to induce psychosis and some individuals may show 20 greater sensitivity than others. The direct effects of hallucinogenic drugs are not usually classified as psychosis, as long as they abate when the drug is metabolised from the body. Chronic psychological stress is also known to precipitate psychotic states, however the exact mechanism is uncertain. Psychosis triggered by stress in the absence of any other mental illness is known as brief reactive psychosis. Psychosis is thus a descriptive term for a complex group of behaviours and experiences. Individuals with schizophrenia can have long periods without psychosis and those with bipolar disorder, 25 or depression, can have mood symptoms without psychosis. [0004] Hallucinations are defined as sensory perception in the absence of external stimuli. Psychotic hallucinations may occur in any of the five senses and can take on almost any form, which may include simple sensations (such as lights, colours, tastes, smells) to more meaningful experiences such as seeing and interacting with fully formed animals and people, hearing voices and complex tactile sensations. Auditory hallucination, particularly the experience of hearing 30 voices, is a common and often prominent feature of psychosis. Hallucinated voices may talk about, or to the person, and may involve several speakers with distinct personas. Auditory hallucinations tend to be particularly distressing when they are derogatory, commanding or preoccupying. [0005] Psychosis may involve delusional or paranoid beliefs, classified into primary and secondary types. Primary delusions are defined as arising out-of-the-blue and not being comprehensible in terms of normal mental processes, 35 whereas secondary delusions may be understood as being influenced by the person’s background or current situation, that is, represent a delusional interpretation of a "real" situation. Thought disorder describes an underlying disturbance to conscious thought and is classified largely by its effects on the content and form of speech and writing. Affected persons may also show pressure of speech (speaking incessantly and quickly), derailment or flight of ideas (switching topic mid-sentence or inappropriately), thought blocking, rhyming or punning. Psychotic episodes may vary in duration 40 from individuals. In brief, reactive psychosis, the psychotic episode is commonly related directly to a specific stressful life event, so patients spontaneously recover normal functioning, usually within two weeks. In some rare cases, individuals may remain in a state of full blown psychosis for many years, or perhaps have attenuated psychotic symptoms (such as low intensity hallucinations) present at most times. [0006] Psychoses exact a tremendous emotional and economic toll on the patients, their families, and society as a 45 whole.