Lurasidone is FDA approved for the treatment of schizophrenia and depressive episodes associated with bipolar I disorder. It has not yet received regulatory approval in the UK. It received EMA approval on January 24, 2014. It was launched in Canada for the treatment of schizophrenia in September 2012, Health Canada giving their Summary Basis of Decision (SBD) as favourable on October 15, 2012. Switzerland is the first and only European country so far where lurasidone is approved for schizophrenia.
In July 2013 lurasidone received approval for bipolar I depression. Few available atypical antipsychotics are known to possess antidepressant efficacy in bipolar disorder (with the notable exceptions being quetiapine,olanzapine and possibly asenapine) as a monotherapy, even though the majority of atypical antipsychotics are known to possess significant antimanic activity, which is yet to be clearly demonstrated for lurasidone.
Lurasidone has completed phase III clinical trial for extended use study in India, although it is not yet approved in India. Lurasidone is not approved by the Food and Drug Administration (FDA) for the treatment of behavior disorders in older adults with dementia.
As with other atypical neuroleptics, lurasidone should be used with caution in the elderly because it puts them at an increased risk for a stroke or transient ischemic attack; however, these risks are not likely to be greater than those associated with antipsychotics of other classes. Similarly, lurasidone should not be used to treat dementia-related psychosis, as evidence has shown increased mortality with its use.
Lurasidone is metabolized in the liver via the enzymeCYP3A4. This means that its plasma concentrations may be increased when combined with CYP3A4 inhibitors like ketoconazole or grapefruit juice, possibly leading to more side effects. Co-administration of CYP3A4 inducers like rifampicin or St. John's wort can reduce plasma levels and consequently decrease the effects of the drug.
The large scale synthesis of lurasidone began with the bis-mesylation of commercially available diol 1 to furnish disulfone 2. Dialkylation of piperazine3 with disulfone 2 under basic conditions afforded spirocyclic tetralkyl ammonium species 4. By subjecting tetralkyl ammonium salt 4 to basic conditions in the presence of succinimide5 an interesting regioselective ring-opening alkylation reaction occurs to form the 1,2-trans-substituted cyclohexane motif of lurasidone. Finally, exposure of lurasidone to hydrochloric acid provided the lurasidone hydrochloride salt.
^Meyer, Jonathan M; Loebel, Antony D; Schweizer, Edward (2009). "Lurasidone: A new drug in development for schizophrenia". Expert Opinion on Investigational Drugs18 (11): 1715–26. doi:10.1517/13543780903286388. PMID19780705.
^Young, Allan H.; McElroy, Susan L.; Bauer, Michael; Philips, Nabil; Chang, William; Olausson, Bengt; Paulsson, Björn; Brecher, Martin; EMBOLDEN I (Trial 001) Investigators (2010). "A Double-Blind, Placebo-Controlled Study of Quetiapine and Lithium Monotherapy in Adults in the Acute Phase of Bipolar Depression (EMBOLDEN I)". The Journal of Clinical Psychiatry71 (2): 150–62. doi:10.4088/JCP.08m04995gre. PMID20122369.
^Suppes, Trisha; Datto, Catherine; Minkwitz, Margaret; Nordenhem, Arvid; Walker, Chris; Darko, Denis (2010). "Effectiveness of the extended release formulation of quetiapine as monotherapy for the treatment of acute bipolar depression". Journal of Affective Disorders121 (1–2): 106–15. doi:10.1016/j.jad.2009.10.007. PMID19903574.
^Tohen, Mauricio; Vieta, E; Calabrese, J; Ketter, TA; Sachs, G; Bowden, C; Mitchell, PB; Centorrino, F; Risser, R; Baker, RW; Evans, AR; Beymer, K; Dube, S; Tollefson, GD; Breier, A (2003). "Efficacy of Olanzapine and Olanzapine-Fluoxetine Combination in the Treatment of Bipolar I Depression". Archives of General Psychiatry60 (11): 1079–88. doi:10.1001/archpsyc.60.11.1079. PMID14609883.
^Tohen, M.; Katagiri, H.; Fujikoshi, S.; Kanba, S. (2013). "Efficacy of olanzapine monotherapy in acute bipolar depression: A pooled analysis of controlled studies". Journal of Affective Disorders149 (1–3): 196–201. doi:10.1016/j.jad.2013.01.022. PMID23485111.
^Corya, Sara A.; Perlis, Roy H.; Keck Jr, Paul E.; Lin, Daniel Y.; Case, Michael G.; Williamson, Doug J.; Tohen, Mauricio F. (2006). "A 24-Week Open-Label Extension Study of Olanzapine-Fluoxetine Combination and Olanzapine Monotherapy in the Treatment of Bipolar Depression". The Journal of Clinical Psychiatry67 (5): 798–806. doi:10.4088/JCP.v67n0514. PMID16841630.
^Azorin, J.M.; Sapin, C.; Weiller, E. (2013). "Effect of asenapine on manic and depressive symptoms in bipolar I patients with mixed episodes: Results from post hoc analyses". Journal of Affective Disorders145 (1): 62–9. doi:10.1016/j.jad.2012.07.013. PMID22868059.
^Cipriani, Andrea; Barbui, Corrado; Salanti, Georgia; Rendell, Jennifer; Brown, Rachel; Stockton, Sarah; Purgato, Marianna; Spineli, Loukia M; Goodwin, Guy M; Geddes, John R (2011). "Comparative efficacy and acceptability of antimanic drugs in acute mania: A multiple-treatments meta-analysis". The Lancet378 (9799): 1306–15. doi:10.1016/S0140-6736(11)60873-8. PMID21851976.
^ abcdefIshiyama, Takeo; Tokuda, Kumiko; Ishibashi, Tadashi; Ito, Akira; Toma, Satoko; Ohno, Yukihiro (2007). "Lurasidone (SM-13496), a novel atypical antipsychotic drug, reverses MK-801-induced impairment of learning and memory in the rat passive-avoidance test". European Journal of Pharmacology572 (2–3): 160–70. doi:10.1016/j.ejphar.2007.06.058. PMID17662268.
^Enomoto, T; Ishibashi, T; Tokuda, K; Ishiyama, T; Toma, S; Ito, A (2008). "Lurasidone reverses MK-801-induced impairment of learning and memory in the Morris water maze and radial-arm maze tests in rats". Behavioural Brain Research186 (2): 197–207. doi:10.1016/j.bbr.2007.08.012. PMID17881065.
^Ishibashi, T.; Horisawa, T.; Tokuda, K.; Ishiyama, T.; Ogasa, M.; Tagashira, R.; Matsumoto, K.; Nishikawa, H.; Ueda, Y.; Toma, S.; Oki, H.; Tanno, N.; Saji, I.; Ito, A.; Ohno, Y.; Nakamura, M. (2010). "Pharmacological Profile of Lurasidone, a Novel Antipsychotic Agent with Potent 5-Hydroxytryptamine 7 (5-HT7) and 5-HT1A Receptor Activity". Journal of Pharmacology and Experimental Therapeutics334 (1): 171–81. doi:10.1124/jpet.110.167346. PMID20404009.
^Ding, Hong X.; Liu, Kevin K.-C.; Sakya, Subas M.; flick, Andrew C.; O'Donnell, Christopher J. (6 April 2013). "Synthetic approaches to the 2011 new drugs". Bioorganic & Medicinal Chemistry (elsevier) 21: 2795–2825. doi:10.1016/j.bmc.2013.02.061.|accessdate= requires |url= (help)
^JP 2006282527, YAGI HIDEKI; KODERA TAKAHIRO; KURUMAYA MASAHIKO; TANAKA KAZUYUKI, "CYCLOHEXANE DERIVATIVE AND METHOD FOR PRODUCING THE SAME", published 2006-10-19
^US patent 20110263847, Ae Nobuyuki and Fujiwara Yuji, "Process of a Quaternary Ammonium Salt", issued 2011-10-27
^WO 2005009999, KAKIYA YUZO; ODA MAYUMI, "PROCESS FOR PRODUCING IMIDE COMPOUND", published 2005-02-03