Combination product for the treatment of neurological and/or psychiatric disorders

Abstract

Combination product for the treatment of neurological and/or psychiatric disorders The present application provides a combination product for the treatment and/or prevention of psychiatric and/or neurological disorders. The combination product comprises (i) a compound which promotes neurogenesis and has hallucinogenic and/or psychedelic side effects, and (ii) a 5-HT2A receptor antagonist which alleviates and/or removes the hallucinogenic and/or psychedelic side effects caused by the first compound.

1 . A pharmaceutical combination product comprising:
 (i) a compound described by the following formula (I):   
       
         
           
           
               
               
           
         
         wherein, 
         R 1  is selected from the group consisting of methyl, ethyl, n-propyl, allyl and isopropyl; 
         R 2  is selected from the group consisting of methyl, ethyl, n-propyl, allyl and isopropyl; 
         R 3  is selected from the group consisting of hydrogen, methoxy, methyl, hydroxy and a halogen; and 
         R 4  is selected from the group consisting of hydrogen, hydroxy, phosphoryloxy and acetoxy; 
         each R 5  is independently selected from the group consisting of deuterium (2H) and protium ('H); and
 (ii) a 5-HT2A receptor antagonist; 
 for use as a medicament. 
 
       
     
     
         2 . A pharmaceutical combination product comprising:
 (i) a compound described by the following formula (I):   
       
         
           
           
               
               
           
         
         wherein, 
         R 1  is selected from the group consisting of methyl, ethyl, n-propyl, allyl and isopropyl; 
         R 2  is selected from the group consisting of methyl, ethyl, n-propyl, allyl and isopropyl; 
         R 3  is selected from the group consisting of hydrogen, methoxy, methyl, hydroxy and a halogen; and 
         R 4  is selected from the group consisting of hydrogen, hydroxy, phosphoryloxy and acetoxy; 
         each R 5  is independently selected from the group consisting of deuterium (2H) and protium ('H); 
         and
 (ii) a 5-HT2A receptor antagonist; 
 for use in the treatment and/or prevention of psychiatric and/or neurological disorders. 
 
       
     
     
         3 . The combination product for use according to anyone of  claims 1 - 2  wherein the compound described by formula (I) is selected from the group consisting of N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, N,N-diethyltryptamine, N,N-dipropyltryptamine and N,N-diisopropyltryptamine. 
     
     
         4 . The combination product for use according to any one of  claims 1 - 3  wherein the 5-HT2A receptor antagonist is selected from the group consisting of Methiothepin, Ritanserin, Ketanserin, Flibanserin, Methysergide, Trazodone, Nefazodone, Cinitapride, Cyproheptadine, Brexpiprazole, Cariprazine, Agomelatine, Pimavanserin, Eplivanserin, Volinanserin, Altanserin, Setoperone, LY-367,265, 1-(1-Naphthyl)piperazine, SB 206553, Pirenperone, SB-215505, Metergoline, Deramciclane, Amperozide, Glemanserin, 5-MeO-NBpBrT, Adatanserin, AMDA, Cinanserin, Fananserin, Iferanserin, AC-90179, LY86057, GSK-215083, Cyamemazine, Mesulergine, BF-1, LY215840, Sergolexole, Spiramide, LY53857, Amesergide, LY108742, Pipamperone, LY314228 and 5-I-R91150. 
     
     
         5 . The combination product for use according to any one of  claims 1 - 4  which further comprises a monoamine oxidase inhibitor. 
     
     
         6 . The combination product for use according to any one of  claims 1 - 5  wherein the combination product is a composition, or the compound described by formula (I) and the 5-HT2A receptor antagonist are physically separated. 
     
     
         7 . The combination product for use according to any one of  claims 1 - 5  wherein the combination product comprises:
 (a) a compound described by formula (I) and instructions on how to administer the compound described by formula (I) with a 5-HT2A receptor antagonist; or 
 (b) a 5-HT2A receptor antagonist and instructions on how to administer the 5-HT2A receptor antagonist with a compound described by formula (I). 
 
     
     
         8 . The combination product for use according to any one of  claims 1 - 7  wherein the combination product is prepared for oral, sublingual, buccal, intranasal, intravenous, intramuscular, subcutaneous, rectal, transdermal, topical and/or inhalation-mediated administration. 
     
     
         9 . The combination product according to anyone of  claims 2 - 8  for use in the treatment and/or prevention of a disorder selected from the group consisting of acquired brain injury, ataxia, brain tumor, dementia, dystonia, epilepsy, functional and dissociative neurological symptoms, meningitis, motor neuron disease, multiple sclerosis, muscular dystrophy, myalgic encephalomyelitis, Parkinson's disease, progressive supranuclear palsy, Huntington's disease, Alzheimer's disease, fronto-temporal dementia, vascular dementia, cognitive decline associated with aging, spina bifida, hydrocephalus, spinal injury, stroke, Tourette syndrome, transverse myelitis, panic disorder, agoraphobia, social anxiety disorder, phobias, post-traumatic stress disorder, obsessive compulsive disorder, generalized anxiety disorder, bipolar disorder, depression, anorexia nervosa, binge eating disorder, bulimia nervosa, psychosis, schizophrenia, substance addiction and personality disorders. 
     
     
         10 . The combination product for use according to  claim 9 , wherein the disorder is Parkinson's disease and/or Alzheimer's disease, preferably Parkinson's disease. 
     
     
         11 . A kit for use in the treatment and/or prevention of psychiatric and/or neurological disorders comprising the combination product according to any one of  claims 1 - 7 . 
     
     
         12 . The combination product for use according to any one of  claims 1 - 10 , wherein the 5-HT2A receptor antagonist alleviates or eliminates the hallucinogenic and/or psychedelic side effects caused by the compound described by formula (I). 
     
     
         13 . The combination product for use according to any one of  claims 1 - 10  and  12 , wherein the compound described by formula (I) stimulates the proliferation, migration and/or differentiation of neural stem cells. 
     
     
         14 . The combination product for use according to any one of  claims 1 - 10  and  12 - 13 , wherein the combination product is administered at least two times, preferably more than two times. 
     
     
         15 . The combination product for use according to any one of  claims 1 - 10  and  12 - 14 , wherein the compound described by formula (I) exerts a neuroprotective and anti-inflammatory effect thereby preventing neural cell degeneration, neural cell death and/or inflammatory responses associated with neural cell degeneration and/or death.