DOCSLIB.ORG

Human Neurogenesis Assay: Modafinil + Buspirone

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

US 20080171 750A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2008/0171750 A1 Barlow et al. (43) Pub. Date: Jul. 17, 2008 (54) MODULATION OF NEUROGENESIS WITH Related U.S. Application Data USE OF MODAFNL (60) Provisional application No. 60/884,584, filed on Jan. (75) Inventors: Carrolee Barlow, Del Mar, CA 11, 2007. (US); Todd A. Carter, San Diego, CA (US); Andrew Morse, San Publication Classification Diego, CA (US); Kai Treuner, San Diego, CA (US); Kym I. Lorrain, (51) Int. Cl. San Diego, CA (US) A 6LX 3L/2197 (2006.01) A6II 3/165. (2006.01) Correspondence Address: A6IP 25/00 (2006.01) TOWNSEND AND TOWNSEND AND CREW, LLP (52) U.S. Cl. .................................... 514/252.18; 514/618 TWO EMBARCADERO CENTER, EIGHTH FLOOR (57) ABSTRACT SAN FRANCISCO, CA 94111-3834 The instant disclosure describes methods for treating diseases (73) Assignee: BrainCells, Inc., San Diego, CA and conditions of the central and peripheral nervous system (US) by stimulating or increasing neurogenesis. The disclosure includes compositions and methods based on use of modafi (21) Appl. No.: 11/972,467 nil, optionally in combination with one or more other neuro genic agents, to stimulate or activate the formation of new (22) Filed: Jan. 10, 2008 nerve cells. Human Neurogenesis Assay: Modafinil + Buspirone Neuronal Differentiation 130 120 -Modafinil 110- - - Buspirone 100 -Modafinil + Buspirone 10-8.5 10-8.0 107.5 10-7.0 10-6.5 10-6.0 10-5.5 10-5.0 10-4.5 10-40 Conc (M) Patent Application Publication Jul. 17, 2008 Sheet 1 of 8 US 2008/0171 750 A1 Figure 1: Human Neurogenesis Assay: Modafinil + Buspirone Neuronal Differentiation 130 120 -Modafinil 110- - - Buspirone 100 -Modafinil + Buspirone 90 10-8.5 10-8.0 10-7.5 10-7.0 10-6.5 10-6-0 10-5.5 10-5.0 10-4.5 10-40 Conc (M) Patent Application Publication Jul. 17, 2008 Sheet 2 of 8 US 2008/0171 750 A1 Figure 2: Human Astrocyte Differentiation Assay: Modafinil + Buspirone Astrocyte Differentiation 110 100 - Modafinil + Buspirone 90- - - - - MOdafini 80 -- Buspirone 70 60 50 40 30 20 10 O -1, 10-8.0 10-7.5 10-7.0 10-6.5 10-6.0 10-5.5 10-5.0 10-4.5 10-40 Conc (M) Patent Application Publication Jul. 17, 2008 Sheet 3 of 8 US 2008/0171 750 A1 Figure 3: Human Neurogenesis Assay: Modafinil + MKC-231 Neuronal Differentiation 130 120 - - - - MOdafini 110 - - MKC-231 g - MOCafini + MKC-231 80 70 60 50 40 30 20 10 O -10 10-8.5 10-8.0 10-7.5 10-7.0 10-6.5 10-6.0 10-5.5 10-5.0 104.5 10-4.0 Conc (M) Patent Application Publication Jul. 17, 2008 Sheet 4 of 8 US 2008/0171 750 A1 Figure 4: Human Neurogenesis Assay: Modafinil + Acamprosate Neuronal Differentiation 110 100 Modafinil -- Acamprosate -Modafinil + Acamprosate 70 60 50 40 30 20 10 O 19, 10-8.0 10-7.5 10-7.0 10-6.5 10-6.0 10-5.5 10-5.0 10-4.5 10-40 n-m-m-m-m-m-a--am 10-9.5 10-9.0 10-8.5 10-8.0 10-7.0 10-7.0 10-6.5 10-6.0 10-5.5 10-50 Conc (M) Acamprosate Concentratio: Patent Application Publication Jul. 17, 2008 Sheet 5 of 8 US 2008/0171750 A1 Figure 5: Human Neurogenesis Assay: Modafinil + Antalarmin Neuronal Differentiation 110 ----Modafinil 100 -- Antalarm in -MOCafinil + Antalarmin -1 10-8.5 10-8.0 107.5 10-7.0 10-6.5 10-6.0 10-5.5 10-5.0 104.5 10-40 Conc (M) Patent Application Publication Jul. 17, 2008 Sheet 6 of 8 US 2008/0171750 A1 Figure 6: Human Neurogenesis Assay: MOCafinil + MKC-231 Neuronal Differentiation 110 ----MOCafinil 100 90 -- AZasetron 80 -Modafinil + AZasetron 70 60 50 40 30 20 10 19, 10-8.0 107.5 10-7.0 10-6.5 10-6.0 10-5.5 10-5.0 104.5 10-40 Conc (M) Patent Application Publication Jul. 17, 2008 Sheet 7 of 8 US 2008/0171750 A1 Figure 7: Human Neurogenesis Assay: Modafinil + Serotonin (model for Serotonin Reuptake inhibitor) NeurOnal Differentiation 110 100 Modafinil -- Serotonin 8 - Modafinil + Serotonin 70 60 50 40 30 2O 10 O 19, 10-8.0 10-7.5 10-7.0 10-6.5 10-6.0 10-5.5 10-5.0 10-4.5 10-40 Conc (M) Patent Application Publication Jul. 17, 2008 Sheet 8 of 8 US 2008/0171 750 A1 Figure 8: Human Neurogenesis Assay: Modafinil and Armodafinil Neuronal Differentiation - MOOdafini ' ' ' 'Armodafinil 5 O - 19, 10-8.0 10-7.5 10-7.0 10-6.5 10-6.0 10-5.5 10-50 10-4.5 10-40 Conc (M) US 2008/0171 750 A1 Jul. 17, 2008 MODULATION OF NEUROGENESIS WITH of the central and/or peripheral nervous systems. In other USE OF MODAFNL embodiments, the disclosed methods are used to improve cognitive outcomes and mood disorders. CROSS-REFERENCES TO RELATED 0006. In one aspect, methods of modulating, such as by APPLICATIONS stimulating or increasing, neurogenesis are disclosed. The 0001. This application claims priority benefit under 35 neurogenesis may be at the level of a cell or tissue. The cellor U.S.C. S 119(e) to U.S. Provisional Patent Application No. tissue may be present in an animal Subject or a human being, 60/884,584, titled: “MODULATION OF NEUROGENESIS or alternatively be in an in vitro or ex vivo setting. In some WITH USE OF MODAFINIL filed Jan. 11, 2007, the dis embodiments, neurogenesis is stimulated or increased in a closure of which is hereby incorporated by reference in it’s neural cell or tissue, such as that of the central or peripheral entirety for all purposes. nervous system of an animal or human being. In cases of an animal or human, the methods may be practiced in connection FIELD OF THE DISCLOSURE with one or more disease, disorder, or condition of the ner Vous system as present in the animal or human Subject. Thus, 0002 The instant disclosure relates to methods for treating embodiments disclosed herein include methods of treating a diseases and conditions of the central and peripheral nervous disease, disorder, or condition by administering modafinil, or system by stimulating or increasing neurogenesis by use of a prodrug thereof, hereinafter referred to as a “modafinil modafinil (CAS RN 68.693-11-8) or a prodrug thereof, such agent. A modafinil agent may beformulated or used alone, or as in combination with a neurogenic agent. The disclosure in combination with one or more additional neurogenic includes methods based on the application of modafinil, or a agents. prodrug thereof, optionally in combination with a neurogenic 0007 Modafinil has a structure represented by Formula I: agent with activity to stimulate or activate the formation of new nerve cells. I BACKGROUND OF THE DISCLOSURE O O 0003) Neurogenesis is a vital process in the brains of ani mals and humans, whereby new nerve cells are continuously S generated throughout the lifespan of the organism. The newly NH2, born cells are able to differentiate into functional cells of the central nervous system and integrate into existing neural cir cuits in the brain. Neurogenesis is known to persist through out adulthood in two regions of the mammalian brain: the subventricular Zone (SVZ) of the lateral ventricles and the dentate gyrus of the hippocampus. In these regions, multipo 0008 Modafinil can also be represented by the chemical tent neural progenitor cells (NPCs) continue to divide and formula C5H5NOS and is also referred to as moderateafi give rise to new functional neurons and glial cells (for review nil, modiodal, provigil, or 2-benzhydrylsulfinylethanamide. Gage 2000). It has been shown that a variety of factors can Related to modafinil is armodafinil (Nuvigile), a eurogeric stimulate adult hippocampal neurogenesis, e.g., adrenalec drug produced by the pharmaceutical company Cephalon Inc. tomy, Voluntary exercise, enriched environment, hippocam Armodafinil is the R-enantionmer of modafinil (i.e., (-)-2- pus dependent learning and anti-depressants (Yehuda 1989, (R)-(diphenylmethyl)-sulfinyl)acetamide. van Praag 1999, Brown J 2003, Gould 1999, Malberg 2000, 0009 While modafinil and armodafinil have been Santarelli 2003). Other factors, such as adrenal hormones, observed to have neurogenic activity as described herein, they stress, age and drugs of abuse negatively influence neurogen have also been observed to reduced or minimized amounts of esis (Cameron 1994, McEwen 1999, Kuhn 1996, Eisch astrogenesis caused by an agent with greater neurogenic 2004). activity. Thus the disclosure may be practiced with the use of 0004 Citation of the above documents is not intended as a combination of a modafinil agent and another neurogenic an admission that any of the foregoing is pertinent prior art. agent, including a neurogenic agent which produces levels of All statements as to the date or representation as to the con astrogenesis that is advantageously reduced or minimized by tents of these documents is based on the information available the use of a modafinil agent. Of course the disclosure also to the applicant and does not constitute any admission as to includes use of a modafinil agent alone. For example, modafi the correctness of the dates or contents of these documents. nil and/or armodafinil may be used alone or in combination with one more other neurogenic agents. Whether alone or in BRIEF SUMMARY OF THE DISCLOSURE combination with another neurogenic agent, the disclosure 0005 Disclosed herein are compositions and methods for may be practiced based on use of a modafinil agent as a the prophylaxis and treatment of diseases, conditions and “direct' agent, in that it has direct activity via interaction with injuries of the central and peripheral nervous systems by its receptor(s) in cells, or as an “indirect agent in that a stimulating or increasing neurogenesis.
Recommended publications
  • Analysis of Drugs Manual September 2019

    Analysis of Drugs Manual September 2019

    Drug Enforcement Administration Office of Forensic Sciences Analysis of Drugs Manual September 2019 Date Posted: 10/23/2019 Analysis of Drugs Manual Revision: 4 Issue Date: September 5, 2019 Effective Date: September 9, 2019 Approved By: Nelson A. Santos Table of Contents CHAPTER 1 – QUALITY ASSURANCE ......................................................................... 3 CHAPTER 2 – EVIDENCE ANALYSIS ......................................................................... 93 CHAPTER 3 – FIELD ASSISTANCE .......................................................................... 165 CHAPTER 4 – FINGERPRINT AND SPECIAL PROGRAMS ..................................... 179 Appendix 1A – Definitions ........................................................................................... 202 Appendix 1B – Acronyms and Abbreviations .............................................................. 211 Appendix 1C – Instrument Maintenance Schedule ..................................................... 218 Appendix 1D – Color Test Reagent Preparation and Procedures ............................... 224 Appendix 1E – Crystal and Precipitate Test Reagent Preparation and Procedures .... 241 Appendix 1F – Thin Layer Chromatography................................................................ 250 Appendix 1G – Qualitative Method Modifications ........................................................ 254 Appendix 1H – Analytical Supplies and Services ........................................................ 256 Appendix 2A – Random Sampling Procedures
  • Modafinil Tablets

    Modafinil Tablets

    PRODUCT MONOGRAPH INCLUDING PATIENT MEDICATION INFORMATION PrAURO-MODAFINIL Modafinil Tablets 100 mg House Standard Central Nervous System Stimulant Auro Pharma Inc. 3700 Steeles Avenue West, Suite # 402 Date of Revision: Woodbridge, ON, L4L 8K8, August 8, 2019. CANADA Submission Control Number: 230314 Page 1 of 41 Table of Contents PART I: HEALTH PROFESSIONAL INFORMATION ......................................................... 3 SUMMARY PRODUCT INFORMATION .................................................................... 3 INDICATIONS AND CLINICAL USE .......................................................................... 3 CONTRAINDICATIONS ............................................................................................... 4 WARNINGS AND PRECAUTIONS .............................................................................. 4 ADVERSE REACTIONS .............................................................................................. 12 DRUG INTERACTIONS .............................................................................................. 16 DOSAGE AND ADMINISTRATION .......................................................................... 19 OVERDOSAGE ............................................................................................................ 21 ACTION AND CLINICAL PHARMACOLOGY ........................................................ 21 STORAGE AND STABILITY ...................................................................................... 23 DOSAGE FORMS, COMPOSITION AND PACKAGING
  • Lifestyle Drugs” for Men and Women

    Lifestyle Drugs” for Men and Women

    Development of “Lifestyle Drugs” for Men and Women Armin Schultz CRS - Clinical Research Services Mannheim GmbH AGAH Annual Meeting 2012, Leipzig, March 01 - 02 Lifestyle drugs Smart drugs, Quality-of-life drugs, Vanity drugs etc. Lifestyle? Lifestyle-Drugs? Active development? Discovery by chance? AGAH Annual Meeting 2012, Leipzig, March 01 - 02 Lifestyle A lifestyle is a characteristic bundle of behaviors that makes sense to both others and oneself in a given time and place, including social relations, consumption, entertainment, and dress. The behaviors and practices within lifestyles are a mixture of habits, conventional ways of doing things, and reasoned actions „Ein Lebensstil ist [...] der regelmäßig wiederkehrende Gesamtzusammenhang der Verhaltensweisen, Interaktionen, Meinungen, Wissensbestände und bewertenden Einstellungen eines Menschen“ (Hradil 2005: 46) Different definitions in social sciences, philosophy, psychology or medicine AGAH Annual Meeting 2012, Leipzig, March 01 - 02 Lifestyle Many “subdivisions” LOHAS: “Lifestyles of Health and Sustainability“ LOVOS: “Lifestyles of Voluntary Simplicity“ SLOHAS: “Slow Lifestyles of Happiness and Sustainability” PARKOS: “Partizipative Konsumenten“ ……. ……. ……. AGAH Annual Meeting 2012, Leipzig, March 01 - 02 Lifestyle drugs Lifestyle drug is an imprecise term commonly applied to medications which treat non-life threatening and non-painful conditions such as baldness, impotence, wrinkles, or acne, without any medical relevance at all or only minor medical relevance relative to others. Desire for increase of personal well-being and quality of life It is sometimes intended as a pejorative, bearing the implication that the scarce medical research resources allocated to develop such drugs were spent frivolously when they could have been better spent researching cures for more serious medical conditions.
  • Phosphodiesterase Type 5 Inhibitor Sildenafil Decreases the Proinflammatory Chemokine CXCL10 in Human Cardiomyocytes and in Subjects with Diabetic Cardiomyopathy

    Phosphodiesterase Type 5 Inhibitor Sildenafil Decreases the Proinflammatory Chemokine CXCL10 in Human Cardiomyocytes and in Subjects with Diabetic Cardiomyopathy

    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Archivio della ricerca- Università di Roma La Sapienza Inflammation, Vol. 39, No. 3, June 2016 (# 2016) DOI: 10.1007/s10753-016-0359-6 ORIGINAL ARTICLE Phosphodiesterase Type 5 Inhibitor Sildenafil Decreases the Proinflammatory Chemokine CXCL10 in Human Cardiomyocytes and in Subjects with Diabetic Cardiomyopathy Luigi Di Luigi,1 Clarissa Corinaldesi,1 Marta Colletti,1 Sabino Scolletta,2 Cristina Antinozzi,1 Gabriella B. Vannelli,3 Elisa Giannetta,4 Daniele Gianfrilli,4 Andrea M. Isidori,4 Silvia Migliaccio,1 Noemi Poerio,5 Maurizio Fraziano,5 Andrea Lenzi,4 and Clara Crescioli1,6 Abstract—T helper 1 (Th1) type cytokines and chemokines are bioactive mediators in inflammation underling several diseases and co-morbid conditions, such as cardiovascular and metabolic disorders. Th1 chemokine CXCL10 participates in heart damage initiation/progression; cardioprotection has been recently associated with sildenafil, a type 5 phosphodiesterase inhibitor. We aimed to evaluate the effect of sildenafil on CXCL10 in inflammatory conditions associated with diabetic cardiomyopathy. We analyzed: CXCL10 gene and protein in human cardiac, endothelial, and immune cells challenged by pro-inflammatory stimuli with and without sildenafil; serum CXCL10 in diabetic subjects at cardiomy- opathy onset, before and after 3 months of treatment with sildenafil vs. placebo. Sildenafil significantly −7 decreased CXCL10 protein secretion (IC50 =2.6×10 ) and gene expression in human cardiomyocytes and significantly decreased circulating CXCL10 in subjects with chemokine basal level ≥ 930 pg/ml, the cut-off value as assessed by ROC analysis. In conclusion, sildenafil could be a pharmacologic tool to control CXCL10-associated inflammation in diabetic cardiomyopathy.
  • [123I]FP-CIT SPECT in Atypical Degenerative Parkinsonism

    [123I]FP-CIT SPECT in Atypical Degenerative Parkinsonism

    CONTRAST AGENT EVALUATION [123I]FP-CIT SPECT in atypical degenerative parkinsonism One of the most widely used techniques to support the clinical diagnosis of Parkinson’s disease is the SPECT scan with [123I]FP-CIT. This tracer binds reversibly and visualizes the striatal presynaptic dopamine transporters. Several uncertainties remain on the value of [123I]FP-CIT and SPECT in atypical degenerative parkinsonian syndromes. In this concise review, we discuss the contribution of SPECT and [123I]FP-CIT in supporting the clinical diagnosis of Parkinson’s disease and their role in the differential diagnosis of Parkinson’s disease and atypical degenerative parkinsonism. The chemistry, pharmacodynamics and pharmacokinetics of [123I]FP-CIT are also discussed. 1,2,3 KEywordS: atypical degenerative parkinsonism n FP-CIT n ioflupane n SPECT Ioannis U Isaias* , Giorgio Marotta4, Gianni Pezzoli2, Parkinson’s disease (PD) is the second most dystonic tremor [15] and psychogenic parkin- Osama Sabri5 [1] [16,17] 5,6 common neurodegenerative disorder , yet sonism . In this concise review, we will & Swen Hesse 123 early accurate diagnosis remains challenging. discuss the role of SPECT and [ I]FP-CIT in 1Università degli Studi di Milano, The estimated prevalence of PD is 0.5–1% in supporting the clinical diagnosis of PD and its Dipartimento di Fisiologia Umana, those aged 65–69 years and 1–3% in those aged differential diagnosis with ADP. Milano, Italy 2Centro per la Malattia di Parkinson e i ≥80 years [1]. Although the clinical diagnosis of Disturbi del Movimento,
  • (19) United States (12) Patent Application Publication (10) Pub

    (19) United States (12) Patent Application Publication (10) Pub

    US 20130289061A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2013/0289061 A1 Bhide et al. (43) Pub. Date: Oct. 31, 2013 (54) METHODS AND COMPOSITIONS TO Publication Classi?cation PREVENT ADDICTION (51) Int. Cl. (71) Applicant: The General Hospital Corporation, A61K 31/485 (2006-01) Boston’ MA (Us) A61K 31/4458 (2006.01) (52) U.S. Cl. (72) Inventors: Pradeep G. Bhide; Peabody, MA (US); CPC """"" " A61K31/485 (201301); ‘4161223011? Jmm‘“ Zhu’ Ansm’ MA. (Us); USPC ......... .. 514/282; 514/317; 514/654; 514/618; Thomas J. Spencer; Carhsle; MA (US); 514/279 Joseph Biederman; Brookline; MA (Us) (57) ABSTRACT Disclosed herein is a method of reducing or preventing the development of aversion to a CNS stimulant in a subject (21) App1_ NO_; 13/924,815 comprising; administering a therapeutic amount of the neu rological stimulant and administering an antagonist of the kappa opioid receptor; to thereby reduce or prevent the devel - . opment of aversion to the CNS stimulant in the subject. Also (22) Flled' Jun‘ 24’ 2013 disclosed is a method of reducing or preventing the develop ment of addiction to a CNS stimulant in a subj ect; comprising; _ _ administering the CNS stimulant and administering a mu Related U‘s‘ Apphcatlon Data opioid receptor antagonist to thereby reduce or prevent the (63) Continuation of application NO 13/389,959, ?led on development of addiction to the CNS stimulant in the subject. Apt 27’ 2012’ ?led as application NO_ PCT/US2010/ Also disclosed are pharmaceutical compositions comprising 045486 on Aug' 13 2010' a central nervous system stimulant and an opioid receptor ’ antagonist.
  • Modafinil and Modafinil Analogues: Free Radical Mechanism of the Eugeroic and Cognitive Enhancment Effect Clifford Fong

    Modafinil and Modafinil Analogues: Free Radical Mechanism of the Eugeroic and Cognitive Enhancment Effect Clifford Fong

    Modafinil and modafinil analogues: free radical mechanism of the eugeroic and cognitive enhancment effect Clifford Fong To cite this version: Clifford Fong. Modafinil and modafinil analogues: free radical mechanism of the eugeroic and cognitive enhancment effect. [Research Report] Eigenenergy. 2018. hal-01933737 HAL Id: hal-01933737 https://hal.archives-ouvertes.fr/hal-01933737 Submitted on 24 Nov 2018 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Modafinil and modafinil analogues: free radical mechanism of the eugeroic and cognitive enhancment effect Clifford W. Fong Eigenenergy, Adelaide, South Australia. Keywords: Modafinil, modafinil-like analogues, eugeroic effect, cognitive enhancement, free radicals, quantum mechanics Abbreviations Dopamine DA, dopamine transporter DAT, Dissociative electron transfer or attachment DET, Linear free energy relationship LFER, free energy of water desolvation ΔG desolv,CDS , lipophilicity free energy ΔG lipo,CDS, cavity dispersion solvent structure of the first solvation shell CDS, highest occupied molecular orbital HOMO, lowest unoccupied molecular orbital LUMO, multiple correlation coefficient R 2, the F test of significance, standards errors for the estimate (SEE) and standard errors of the variables SE(ΔG desolCDS ), SE(ΔG lipoCDS ), SE(Dipole Moment), SE (Molecular Volume), transition state TS, reactive oxygen species ROS.
  • Cannabigerol Is a Potential Therapeutic Agent in a Novel Combined Therapy for Glioblastoma

    Cannabigerol Is a Potential Therapeutic Agent in a Novel Combined Therapy for Glioblastoma

    cells Article Cannabigerol Is a Potential Therapeutic Agent in a Novel Combined Therapy for Glioblastoma Tamara T. Lah 1,2,3,*, Metka Novak 1, Milagros A. Pena Almidon 4, Oliviero Marinelli 4 , Barbara Žvar Baškoviˇc 1, Bernarda Majc 1,3, Mateja Mlinar 1, Roman Bošnjak 5, Barbara Breznik 1 , Roby Zomer 6 and Massimo Nabissi 4 1 Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, 1000 Ljubljana, Slovenia; [email protected] (M.N.); [email protected] (B.Ž.B.); [email protected] (B.M.); [email protected] (M.M.); [email protected] (B.B.) 2 Faculty of Chemistry and Chemical Technology, University of Ljubljana, 1000 Ljubljana, Slovenia 3 Jožef Stefan International Postgraduate School, 1000 Ljubljana, Slovenia 4 School of Pharmacy, Experimental Medicine Section, University of Camerino, 62032 Camerino, Italy; [email protected] (M.A.P.A.); [email protected] (O.M.); [email protected] (M.N.) 5 Department of Neurosurgery, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia; [email protected] 6 MGC Pharmaceuticals d.o.o., 1000 Ljubljana, Slovenia; [email protected] * Correspondence: [email protected]; Tel.: +386-41-651-629 Simple Summary: Among primary brain tumours, glioblastoma is the most aggressive. As early relapses are unavoidable despite standard-of-care treatment, the cannabinoids delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) alone or in combination have been suggested as a combined treatment strategy for glioblastomas. However, the known psychoactive effects of THC hamper its medical applications in these patients with potential cognitive impairment due to the progression of the Citation: Lah, T.T.; Novak, M.; Pena Almidon, M.A.; Marinelli, O.; disease.
  • (Orion) 5 Mg Tablets Buspirone (Orion) 10 Mg Tablets

    (Orion) 5 Mg Tablets Buspirone (Orion) 10 Mg Tablets

    NEW ZEALAND DATA SHEET 1. PRODUCT NAME Buspirone (Orion) 5 mg tablets Buspirone (Orion) 10 mg tablets 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each tablet contains 5 mg buspirone hydrochloride. Each tablet contains 10 mg buspirone hydrochloride. Excipient with known effect: 5 mg tablet: Each tablet contains 59.5 mg lactose (as monohydrate) 10 mg tablet: Each tablet contains 118.9 mg lactose (as monohydrate). For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Tablet. 5 mg tablet: White or almost white, oval tablets debossed with ‘ORN 30’ on one side and a score on the other side. The tablet can be divided into equal doses. 10 mg tablet: White or almost white, oval tablets debossed with ‘ORN 31’ on one side and a score on the other side. The tablet can be divided into equal doses. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications Buspirone hydrochloride is indicated for the management of anxiety with or without accompanying depression in adults. Buspirone hydrochloride is indicated for the management of anxiety disorders or the short- term relief of symptoms of anxiety with or without accompanying depression. 4.2 Posology and method of administration The usual starting dose is 5 mg given three times daily. This may be titrated according to the needs of the patient and the daily dose increased by 5 mg increments every two or three days depending upon the therapeutic response to a maximum daily dose of 60 mg. After dosage titration the usual daily dose will be 20 to 30 mg per day in divided doses.
  • MODERN INDICATIONS for the USE of OPIPRAMOL Krzysztof Krysta1, Sławomir Murawiec2, Anna Warchala1, Karolina Zawada3, Wiesław J

    MODERN INDICATIONS for the USE of OPIPRAMOL Krzysztof Krysta1, Sławomir Murawiec2, Anna Warchala1, Karolina Zawada3, Wiesław J

    Psychiatria Danubina, 2015; Vol. 27, Suppl. 1, pp 435–437 Conference paper © Medicinska naklada - Zagreb, Croatia MODERN INDICATIONS FOR THE USE OF OPIPRAMOL Krzysztof Krysta1, Sławomir Murawiec2, Anna Warchala1, Karolina Zawada3, Wiesław J. Cubała4, Mariusz S. Wiglusz4, Katarzyna Jakuszkowiak-Wojten4, Marek Krzystanek5 & Irena Krupka-Matuszczyk1 1Department of Psychiatry and Psychotherapy, Medical University of Silesia, Katowice, Poland 2“Dialogue” Therapy Centre, Warsaw, Poland 3Department of Pneumonology, Medical University of Silesia, Katowice, Poland 4Department of Psychiatry, Medical University of Gdańsk, Gdańsk, Poland 5Department of Rehabilitation Psychiatry, Medical University of Silesia, Katowice, Poland SUMMARY Opipramol is considered as a pharmacological agent that does not fit the classification taking into account the division of antidepressants, antipsychotics and anxiolytics. It has a structure related to tricyclic antidepressants but it has a different mechanism of action, i.e. binding to sigma1 and to sigma2 sites. It has been regarded as an effective drug in general anxiety disorders together with other agents like SSRI`s, SNRI`s, buspirone and pregabalin for many years. It can however also be indicated in other conditions, e.g. it may be used as a premedication in the evening prior to surgery, positive results are also observed in psychopharmacological treatment with opipramol in somatoform disorders, symptoms of depression can be significantly reduced in the climacteric syndrome. The latest data from literature present also certain dangers and side effects, which may result due to opipramol administration. Mania may be induced not only in bipolar patients treated with opipramol, but it can be an adverse drug reaction in generalized anxiety disorder. This analysis shows however that opipramol is an important drug still very useful in different clinical conditions.
  • Uses of Bremelanotide in Therapy for Female Sexual

    Uses of Bremelanotide in Therapy for Female Sexual

    (19) TZZ __T (11) EP 2 916 856 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: A61K 9/00 (2006.01) A61K 38/12 (2006.01) 19.09.2018 Bulletin 2018/38 A61P 15/00 (2006.01) C07K 7/64 (2006.01) (21) Application number: 13851014.4 (86) International application number: PCT/US2013/068386 (22) Date of filing: 05.11.2013 (87) International publication number: WO 2014/071339 (08.05.2014 Gazette 2014/19) (54) USES OF BREMELANOTIDE IN THERAPY FOR FEMALE SEXUAL DYSFUNCTION VERWENDUNG VON BREMELANOTID IN DER THERAPIE VON WEIBLICHER SEXUELLER DYSFUNKTION UTILISATIONS DE BRÉMÉLANOTIDE DANS UNE THÉRAPIE DE DYSFONCTIONNEMENT SEXUEL FÉMININ (84) Designated Contracting States: • "Palatin Technologies Presents Positive Results AL AT BE BG CH CY CZ DE DK EE ES FI FR GB for Phase 2B Bremelanotide Female Sexual GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO Dysfunction Trial", PRNewswire , 8 November PL PT RO RS SE SI SK SM TR 2012 (2012-11-08), XP002757483, Retrieved from the Internet: (30) Priority: 05.11.2012 US 201261722511 P URL:http://www.palatin.com/investors/press 28.02.2013 US 201361770535 P -releases/ [retrieved on 2016-05-09] • ROSEN R C ET AL: "Evaluation of the safety, (43) Date of publication of application: pharmacokineticsand pharmacodynamic effects 16.09.2015 Bulletin 2015/38 of subcutaneously administered PT-141, a melanocortin receptor agonist, in healthy male (73) Proprietor: Palatin Technologies, Inc. subjects and in patients with an inadequate Cranbury NJ 08512 (US) response to Viagra(R)", INTERNATIONAL JOURNAL OF IMPOTENCE RESEARCH, (72) Inventors: STOCKTON, BASINGSTOKE, GB, vol.
  • PHARMACEUTICAL APPENDIX to the TARIFF SCHEDULE 2 Table 1

    PHARMACEUTICAL APPENDIX to the TARIFF SCHEDULE 2 Table 1

    Harmonized Tariff Schedule of the United States (2020) Revision 19 Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE Harmonized Tariff Schedule of the United States (2020) Revision 19 Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 2 Table 1. This table enumerates products described by International Non-proprietary Names INN which shall be entered free of duty under general note 13 to the tariff schedule. The Chemical Abstracts Service CAS registry numbers also set forth in this table are included to assist in the identification of the products concerned. For purposes of the tariff schedule, any references to a product enumerated in this table includes such product by whatever name known.