BRPI0711816A2 - inibidores fosfodiesterase 4 para rehabilitação motora e cognitiva - Google Patents
inibidores fosfodiesterase 4 para rehabilitação motora e cognitiva Download PDFInfo
- Publication number
- BRPI0711816A2 BRPI0711816A2 BRPI0711816-3A BRPI0711816A BRPI0711816A2 BR PI0711816 A2 BRPI0711816 A2 BR PI0711816A2 BR PI0711816 A BRPI0711816 A BR PI0711816A BR PI0711816 A2 BRPI0711816 A2 BR PI0711816A2
- Authority
- BR
- Brazil
- Prior art keywords
- cognitive
- training
- creb
- pde4
- phosphodiesterase
- Prior art date
Links
- 230000001149 cognitive effect Effects 0.000 title claims abstract description 93
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 title claims abstract description 48
- 238000012549 training Methods 0.000 claims abstract description 180
- 238000000034 method Methods 0.000 claims abstract description 95
- 230000006872 improvement Effects 0.000 claims abstract description 57
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 26
- 210000003169 central nervous system Anatomy 0.000 claims abstract description 21
- 230000006735 deficit Effects 0.000 claims abstract description 20
- 230000001537 neural effect Effects 0.000 claims description 66
- 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 claims description 44
- 238000011282 treatment Methods 0.000 claims description 40
- 230000001419 dependent effect Effects 0.000 claims description 36
- 230000002708 enhancing effect Effects 0.000 claims description 33
- 230000002459 sustained effect Effects 0.000 claims description 32
- MSYGAHOHLUJIKV-UHFFFAOYSA-N 3,5-dimethyl-1-(3-nitrophenyl)-1h-pyrazole-4-carboxylic acid ethyl ester Chemical compound CC1=C(C(=O)OCC)C(C)=NN1C1=CC=CC([N+]([O-])=O)=C1 MSYGAHOHLUJIKV-UHFFFAOYSA-N 0.000 claims description 27
- 102000011017 Type 4 Cyclic Nucleotide Phosphodiesterases Human genes 0.000 claims description 27
- 108010037584 Type 4 Cyclic Nucleotide Phosphodiesterases Proteins 0.000 claims description 27
- 241001465754 Metazoa Species 0.000 claims description 25
- 208000010877 cognitive disease Diseases 0.000 claims description 25
- 230000036992 cognitive tasks Effects 0.000 claims description 18
- 241000282414 Homo sapiens Species 0.000 claims description 16
- 239000003112 inhibitor Substances 0.000 claims description 16
- 206010027175 memory impairment Diseases 0.000 claims description 16
- 208000028698 Cognitive impairment Diseases 0.000 claims description 15
- 230000007278 cognition impairment Effects 0.000 claims description 15
- 230000003920 cognitive function Effects 0.000 claims description 15
- HJORMJIFDVBMOB-UHFFFAOYSA-N rolipram Chemical compound COC1=CC=C(C2CC(=O)NC2)C=C1OC1CCCC1 HJORMJIFDVBMOB-UHFFFAOYSA-N 0.000 claims description 14
- 208000014674 injury Diseases 0.000 claims description 13
- 229950005741 rolipram Drugs 0.000 claims description 13
- 208000036626 Mental retardation Diseases 0.000 claims description 12
- 150000001875 compounds Chemical class 0.000 claims description 11
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 230000000638 stimulation Effects 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 6
- 230000008733 trauma Effects 0.000 claims description 6
- 239000002571 phosphodiesterase inhibitor Substances 0.000 claims description 4
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 3
- 229940099471 Phosphodiesterase inhibitor Drugs 0.000 claims description 3
- 230000009395 genetic defect Effects 0.000 claims description 3
- 108010045171 Cyclic AMP Response Element-Binding Protein Proteins 0.000 description 143
- 102000005636 Cyclic AMP Response Element-Binding Protein Human genes 0.000 description 143
- 230000006870 function Effects 0.000 description 61
- 239000003795 chemical substances by application Substances 0.000 description 55
- 241000700159 Rattus Species 0.000 description 47
- 238000002474 experimental method Methods 0.000 description 45
- 239000003981 vehicle Substances 0.000 description 41
- 239000003814 drug Substances 0.000 description 40
- 229940079593 drug Drugs 0.000 description 39
- 230000015654 memory Effects 0.000 description 39
- 230000000694 effects Effects 0.000 description 37
- 230000007787 long-term memory Effects 0.000 description 37
- 230000037361 pathway Effects 0.000 description 37
- 241000700198 Cavia Species 0.000 description 29
- 210000004027 cell Anatomy 0.000 description 28
- 230000006378 damage Effects 0.000 description 28
- 208000029028 brain injury Diseases 0.000 description 27
- 238000012360 testing method Methods 0.000 description 27
- 230000006931 brain damage Effects 0.000 description 25
- 231100000874 brain damage Toxicity 0.000 description 25
- 108090000623 proteins and genes Proteins 0.000 description 25
- 241000699670 Mus sp. Species 0.000 description 24
- 230000013016 learning Effects 0.000 description 24
- 210000004556 brain Anatomy 0.000 description 23
- 208000011580 syndromic disease Diseases 0.000 description 23
- 208000006011 Stroke Diseases 0.000 description 21
- 210000002569 neuron Anatomy 0.000 description 17
- 150000007523 nucleic acids Chemical class 0.000 description 17
- 230000003750 conditioning effect Effects 0.000 description 16
- 230000008449 language Effects 0.000 description 16
- 208000026139 Memory disease Diseases 0.000 description 15
- 241000700605 Viruses Species 0.000 description 15
- 230000014509 gene expression Effects 0.000 description 15
- 208000030886 Traumatic Brain injury Diseases 0.000 description 14
- 102000004169 proteins and genes Human genes 0.000 description 14
- 230000015572 biosynthetic process Effects 0.000 description 13
- 208000035475 disorder Diseases 0.000 description 13
- 238000001647 drug administration Methods 0.000 description 13
- 230000014759 maintenance of location Effects 0.000 description 13
- 238000002347 injection Methods 0.000 description 12
- 239000007924 injection Substances 0.000 description 12
- 230000009529 traumatic brain injury Effects 0.000 description 12
- 230000003416 augmentation Effects 0.000 description 11
- 230000003931 cognitive performance Effects 0.000 description 11
- 230000003190 augmentative effect Effects 0.000 description 10
- 208000024827 Alzheimer disease Diseases 0.000 description 9
- 206010012289 Dementia Diseases 0.000 description 9
- 108091028043 Nucleic acid sequence Proteins 0.000 description 9
- 230000032683 aging Effects 0.000 description 9
- 230000002068 genetic effect Effects 0.000 description 9
- 230000000971 hippocampal effect Effects 0.000 description 9
- 102000039446 nucleic acids Human genes 0.000 description 9
- 108020004707 nucleic acids Proteins 0.000 description 9
- 238000011084 recovery Methods 0.000 description 9
- 206010003805 Autism Diseases 0.000 description 8
- 208000020706 Autistic disease Diseases 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 150000001413 amino acids Chemical group 0.000 description 8
- 230000007774 longterm Effects 0.000 description 8
- 230000007334 memory performance Effects 0.000 description 8
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 description 7
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 description 7
- 208000003174 Brain Neoplasms Diseases 0.000 description 7
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 7
- IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 description 7
- 208000027418 Wounds and injury Diseases 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 description 7
- 230000003925 brain function Effects 0.000 description 7
- 229940095074 cyclic amp Drugs 0.000 description 7
- 239000012634 fragment Substances 0.000 description 7
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 description 7
- 230000001965 increasing effect Effects 0.000 description 7
- 230000006698 induction Effects 0.000 description 7
- 208000015122 neurodegenerative disease Diseases 0.000 description 7
- 108090000765 processed proteins & peptides Proteins 0.000 description 7
- 201000010374 Down Syndrome Diseases 0.000 description 6
- 206010068871 Myotonic dystrophy Diseases 0.000 description 6
- 208000009905 Neurofibromatoses Diseases 0.000 description 6
- 230000004064 dysfunction Effects 0.000 description 6
- 108020001507 fusion proteins Proteins 0.000 description 6
- 102000037865 fusion proteins Human genes 0.000 description 6
- 210000001320 hippocampus Anatomy 0.000 description 6
- 230000001976 improved effect Effects 0.000 description 6
- 208000028867 ischemia Diseases 0.000 description 6
- 201000004931 neurofibromatosis Diseases 0.000 description 6
- 208000020016 psychiatric disease Diseases 0.000 description 6
- 201000000980 schizophrenia Diseases 0.000 description 6
- 230000000946 synaptic effect Effects 0.000 description 6
- 208000023105 Huntington disease Diseases 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 208000018737 Parkinson disease Diseases 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 5
- 208000026106 cerebrovascular disease Diseases 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 239000003623 enhancer Substances 0.000 description 5
- 238000011156 evaluation Methods 0.000 description 5
- 239000012530 fluid Substances 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 230000006403 short-term memory Effects 0.000 description 5
- 210000000225 synapse Anatomy 0.000 description 5
- 238000013518 transcription Methods 0.000 description 5
- 230000035897 transcription Effects 0.000 description 5
- 239000013598 vector Substances 0.000 description 5
- 230000000007 visual effect Effects 0.000 description 5
- 208000009575 Angelman syndrome Diseases 0.000 description 4
- 208000001353 Coffin-Lowry syndrome Diseases 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 206010019196 Head injury Diseases 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- 101000919269 Homo sapiens cAMP-responsive element modulator Proteins 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- 208000006289 Rett Syndrome Diseases 0.000 description 4
- 206010039281 Rubinstein-Taybi syndrome Diseases 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 239000012190 activator Substances 0.000 description 4
- 238000000540 analysis of variance Methods 0.000 description 4
- 230000027455 binding Effects 0.000 description 4
- 102000023732 binding proteins Human genes 0.000 description 4
- 108091008324 binding proteins Proteins 0.000 description 4
- 102100029387 cAMP-responsive element modulator Human genes 0.000 description 4
- 230000002950 deficient Effects 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 230000001939 inductive effect Effects 0.000 description 4
- 230000002045 lasting effect Effects 0.000 description 4
- 201000003723 learning disability Diseases 0.000 description 4
- 230000005923 long-lasting effect Effects 0.000 description 4
- 230000007659 motor function Effects 0.000 description 4
- 230000004770 neurodegeneration Effects 0.000 description 4
- 230000007996 neuronal plasticity Effects 0.000 description 4
- 238000009527 percussion Methods 0.000 description 4
- 102000004196 processed proteins & peptides Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 206010053884 trisomy 18 Diseases 0.000 description 4
- 206010008748 Chorea Diseases 0.000 description 3
- 102100026359 Cyclic AMP-responsive element-binding protein 1 Human genes 0.000 description 3
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 3
- 101000855516 Homo sapiens Cyclic AMP-responsive element-binding protein 1 Proteins 0.000 description 3
- 208000019022 Mood disease Diseases 0.000 description 3
- 206010061296 Motor dysfunction Diseases 0.000 description 3
- 206010029333 Neurosis Diseases 0.000 description 3
- 229920005372 Plexiglas® Polymers 0.000 description 3
- 206010039966 Senile dementia Diseases 0.000 description 3
- 208000002667 Subdural Hematoma Diseases 0.000 description 3
- 206010044686 Trisomy 13 Diseases 0.000 description 3
- 208000006284 Trisomy 13 Syndrome Diseases 0.000 description 3
- 206010049644 Williams syndrome Diseases 0.000 description 3
- 210000004727 amygdala Anatomy 0.000 description 3
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 3
- 201000007201 aphasia Diseases 0.000 description 3
- 230000006399 behavior Effects 0.000 description 3
- 230000030833 cell death Effects 0.000 description 3
- 208000012601 choreatic disease Diseases 0.000 description 3
- 230000001054 cortical effect Effects 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 230000007812 deficiency Effects 0.000 description 3
- 230000008014 freezing Effects 0.000 description 3
- 238000007710 freezing Methods 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 238000007912 intraperitoneal administration Methods 0.000 description 3
- 230000033001 locomotion Effects 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 230000006386 memory function Effects 0.000 description 3
- 230000006993 memory improvement Effects 0.000 description 3
- 238000010369 molecular cloning Methods 0.000 description 3
- 230000037023 motor activity Effects 0.000 description 3
- 208000015238 neurotic disease Diseases 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 230000004911 positive regulation of CREB transcription factor activity Effects 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 230000005855 radiation Effects 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 230000002787 reinforcement Effects 0.000 description 3
- 230000000717 retained effect Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 210000000130 stem cell Anatomy 0.000 description 3
- 230000004936 stimulating effect Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 230000003956 synaptic plasticity Effects 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 230000009261 transgenic effect Effects 0.000 description 3
- 230000014616 translation Effects 0.000 description 3
- 241001430294 unidentified retrovirus Species 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 108700007837 A-CREB Proteins 0.000 description 2
- 208000013824 Acidemia Diseases 0.000 description 2
- 208000010444 Acidosis Diseases 0.000 description 2
- 208000019901 Anxiety disease Diseases 0.000 description 2
- 241000271566 Aves Species 0.000 description 2
- 241000282693 Cercopithecidae Species 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- 206010010305 Confusional state Diseases 0.000 description 2
- 206010010356 Congenital anomaly Diseases 0.000 description 2
- 206010011385 Cri-du-chat syndrome Diseases 0.000 description 2
- 102000053602 DNA Human genes 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 206010012218 Delirium Diseases 0.000 description 2
- 101001098814 Dictyostelium discoideum 3',5'-cyclic-nucleotide phosphodiesterase regA Proteins 0.000 description 2
- 101001117086 Dictyostelium discoideum cAMP/cGMP-dependent 3',5'-cAMP/cGMP phosphodiesterase A Proteins 0.000 description 2
- 101001098806 Dictyostelium discoideum cGMP-specific 3',5'-cGMP phosphodiesterase 3 Proteins 0.000 description 2
- 201000006360 Edwards syndrome Diseases 0.000 description 2
- 241000289695 Eutheria Species 0.000 description 2
- OHCQJHSOBUTRHG-KGGHGJDLSA-N FORSKOLIN Chemical compound O=C([C@@]12O)C[C@](C)(C=C)O[C@]1(C)[C@@H](OC(=O)C)[C@@H](O)[C@@H]1[C@]2(C)[C@@H](O)CCC1(C)C OHCQJHSOBUTRHG-KGGHGJDLSA-N 0.000 description 2
- 201000011240 Frontotemporal dementia Diseases 0.000 description 2
- 208000027472 Galactosemias Diseases 0.000 description 2
- 208000015872 Gaucher disease Diseases 0.000 description 2
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 2
- 208000012029 Isolated congenital microcephaly Diseases 0.000 description 2
- 208000017924 Klinefelter Syndrome Diseases 0.000 description 2
- 241000713666 Lentivirus Species 0.000 description 2
- 208000009625 Lesch-Nyhan syndrome Diseases 0.000 description 2
- 208000002720 Malnutrition Diseases 0.000 description 2
- 208000001804 Monosomy 5p Diseases 0.000 description 2
- 206010068052 Mosaicism Diseases 0.000 description 2
- 206010056886 Mucopolysaccharidosis I Diseases 0.000 description 2
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 2
- 208000012902 Nervous system disease Diseases 0.000 description 2
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 description 2
- 201000009928 Patau syndrome Diseases 0.000 description 2
- 208000000609 Pick Disease of the Brain Diseases 0.000 description 2
- 208000028017 Psychotic disease Diseases 0.000 description 2
- 208000035317 Total hypoxanthine-guanine phosphoribosyl transferase deficiency Diseases 0.000 description 2
- 208000007159 Trisomy 18 Syndrome Diseases 0.000 description 2
- 208000026911 Tuberous sclerosis complex Diseases 0.000 description 2
- 208000026928 Turner syndrome Diseases 0.000 description 2
- 201000004810 Vascular dementia Diseases 0.000 description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 2
- 102000030621 adenylate cyclase Human genes 0.000 description 2
- 108060000200 adenylate cyclase Proteins 0.000 description 2
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 2
- 210000003484 anatomy Anatomy 0.000 description 2
- 230000036506 anxiety Effects 0.000 description 2
- 230000003542 behavioural effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 210000005013 brain tissue Anatomy 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 208000015114 central nervous system disease Diseases 0.000 description 2
- 230000002759 chromosomal effect Effects 0.000 description 2
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 2
- 230000019771 cognition Effects 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 239000004020 conductor Substances 0.000 description 2
- 238000007428 craniotomy Methods 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 230000003001 depressive effect Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 230000003828 downregulation Effects 0.000 description 2
- 230000013020 embryo development Effects 0.000 description 2
- 210000003128 head Anatomy 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 239000007943 implant Substances 0.000 description 2
- 238000002513 implantation Methods 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000010354 integration Effects 0.000 description 2
- 229960002725 isoflurane Drugs 0.000 description 2
- 230000001071 malnutrition Effects 0.000 description 2
- 235000000824 malnutrition Nutrition 0.000 description 2
- 238000007726 management method Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 230000007171 neuropathology Effects 0.000 description 2
- 230000000324 neuroprotective effect Effects 0.000 description 2
- 208000015380 nutritional deficiency disease Diseases 0.000 description 2
- 208000007138 otopalatodigital syndrome type 1 Diseases 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 208000019899 phobic disease Diseases 0.000 description 2
- 239000004926 polymethyl methacrylate Substances 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 201000001726 primary microcephaly Diseases 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 102000021127 protein binding proteins Human genes 0.000 description 2
- 108091011138 protein binding proteins Proteins 0.000 description 2
- 238000001243 protein synthesis Methods 0.000 description 2
- 230000008521 reorganization Effects 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 230000037152 sensory function Effects 0.000 description 2
- 230000035939 shock Effects 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 231100000378 teratogenic Toxicity 0.000 description 2
- 230000003390 teratogenic effect Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 230000002103 transcriptional effect Effects 0.000 description 2
- 208000009999 tuberous sclerosis Diseases 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- 239000013603 viral vector Substances 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- 102000001707 3',5'-Cyclic-AMP Phosphodiesterases Human genes 0.000 description 1
- 108010054479 3',5'-Cyclic-AMP Phosphodiesterases Proteins 0.000 description 1
- 102000021435 AMP binding proteins Human genes 0.000 description 1
- 108091011073 AMP binding proteins Proteins 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 108060003345 Adrenergic Receptor Proteins 0.000 description 1
- 102000017910 Adrenergic receptor Human genes 0.000 description 1
- 208000006888 Agnosia Diseases 0.000 description 1
- 241001047040 Agnosia Species 0.000 description 1
- 206010001939 Aminoaciduria Diseases 0.000 description 1
- 208000000044 Amnesia Diseases 0.000 description 1
- 208000009115 Anorectal Malformations Diseases 0.000 description 1
- 108020005544 Antisense RNA Proteins 0.000 description 1
- 206010003062 Apraxia Diseases 0.000 description 1
- 241000714230 Avian leukemia virus Species 0.000 description 1
- 241001485018 Baboon endogenous virus Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 241000714266 Bovine leukemia virus Species 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- RZZPDXZPRHQOCG-OJAKKHQRSA-O CDP-choline(1+) Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OCC[N+](C)(C)C)O[C@H]1N1C(=O)N=C(N)C=C1 RZZPDXZPRHQOCG-OJAKKHQRSA-O 0.000 description 1
- 108010040163 CREB-Binding Protein Proteins 0.000 description 1
- 102100021975 CREB-binding protein Human genes 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 241000711573 Coronaviridae Species 0.000 description 1
- 208000020406 Creutzfeldt Jacob disease Diseases 0.000 description 1
- 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 description 1
- 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 description 1
- 241000938605 Crocodylia Species 0.000 description 1
- 101710095468 Cyclase Proteins 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- SUZLHDUTVMZSEV-UHFFFAOYSA-N Deoxycoleonol Natural products C12C(=O)CC(C)(C=C)OC2(C)C(OC(=O)C)C(O)C2C1(C)C(O)CCC2(C)C SUZLHDUTVMZSEV-UHFFFAOYSA-N 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- 241000255925 Diptera Species 0.000 description 1
- 238000001061 Dunnett's test Methods 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 108700024394 Exon Proteins 0.000 description 1
- 208000026097 Factitious disease Diseases 0.000 description 1
- 241000714165 Feline leukemia virus Species 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 229920002683 Glycosaminoglycan Polymers 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 208000037357 HIV infectious disease Diseases 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 241000700588 Human alphaherpesvirus 1 Species 0.000 description 1
- 241000701074 Human alphaherpesvirus 2 Species 0.000 description 1
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 1
- 201000001431 Hyperuricemia Diseases 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- 208000032382 Ischaemic stroke Diseases 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 208000009829 Lewy Body Disease Diseases 0.000 description 1
- 201000002832 Lewy body dementia Diseases 0.000 description 1
- 241000282553 Macaca Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241000289419 Metatheria Species 0.000 description 1
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 1
- 241000237852 Mollusca Species 0.000 description 1
- 241000713862 Moloney murine sarcoma virus Species 0.000 description 1
- 208000002678 Mucopolysaccharidoses Diseases 0.000 description 1
- 241000714177 Murine leukemia virus Species 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 101100291013 Mus musculus Met gene Proteins 0.000 description 1
- 206010029350 Neurotoxicity Diseases 0.000 description 1
- 208000014060 Niemann-Pick disease Diseases 0.000 description 1
- 241000714209 Norwalk virus Species 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 108700026244 Open Reading Frames Proteins 0.000 description 1
- 102000003840 Opioid Receptors Human genes 0.000 description 1
- 108090000137 Opioid Receptors Proteins 0.000 description 1
- 241000282579 Pan Species 0.000 description 1
- 241000282320 Panthera leo Species 0.000 description 1
- 102000002508 Peptide Elongation Factors Human genes 0.000 description 1
- 108010068204 Peptide Elongation Factors Proteins 0.000 description 1
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical class NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 1
- 201000011252 Phenylketonuria Diseases 0.000 description 1
- 102000045595 Phosphoprotein Phosphatases Human genes 0.000 description 1
- 108700019535 Phosphoprotein Phosphatases Proteins 0.000 description 1
- 241000709664 Picornaviridae Species 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 241000125945 Protoparvovirus Species 0.000 description 1
- 206010052276 Pseudodementia Diseases 0.000 description 1
- 206010037742 Rabies Diseases 0.000 description 1
- 241000702263 Reovirus sp. Species 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 241000714474 Rous sarcoma virus Species 0.000 description 1
- 208000018030 Rubinstein-Taybi syndrome due to CREBBP mutations Diseases 0.000 description 1
- 241000282849 Ruminantia Species 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 241000543375 Sideroxylon Species 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 208000000389 T-cell leukemia Diseases 0.000 description 1
- 208000028530 T-cell lymphoblastic leukemia/lymphoma Diseases 0.000 description 1
- 208000022292 Tay-Sachs disease Diseases 0.000 description 1
- 206010044221 Toxic encephalopathy Diseases 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 208000037280 Trisomy Diseases 0.000 description 1
- 241000700647 Variola virus Species 0.000 description 1
- 229930003270 Vitamin B Natural products 0.000 description 1
- 241000714205 Woolly monkey sarcoma virus Species 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 239000003570 air Substances 0.000 description 1
- 239000012080 ambient air Substances 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 238000012550 audit Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 230000005978 brain dysfunction Effects 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 108091010966 cAMP binding proteins Proteins 0.000 description 1
- 102000036109 cAMP binding proteins Human genes 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229930003827 cannabinoid Natural products 0.000 description 1
- 239000003557 cannabinoid Substances 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 229960003920 cocaine Drugs 0.000 description 1
- 239000002475 cognitive enhancer Substances 0.000 description 1
- OHCQJHSOBUTRHG-UHFFFAOYSA-N colforsin Natural products OC12C(=O)CC(C)(C=C)OC1(C)C(OC(=O)C)C(O)C1C2(C)C(O)CCC1(C)C OHCQJHSOBUTRHG-UHFFFAOYSA-N 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 239000003184 complementary RNA Substances 0.000 description 1
- 230000001143 conditioned effect Effects 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000003255 drug test Methods 0.000 description 1
- 206010013932 dyslexia Diseases 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000006592 excitoxicity Effects 0.000 description 1
- 230000010326 executive functioning Effects 0.000 description 1
- 230000021824 exploration behavior Effects 0.000 description 1
- 238000013100 final test Methods 0.000 description 1
- 235000019688 fish Nutrition 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 210000001652 frontal lobe Anatomy 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 238000011554 guinea pig model Methods 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 229920000140 heteropolymer Polymers 0.000 description 1
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 208000003906 hydrocephalus Diseases 0.000 description 1
- 208000003532 hypothyroidism Diseases 0.000 description 1
- 230000002989 hypothyroidism Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000003308 immunostimulating effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000000185 intracerebroventricular administration Methods 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 150000008040 ionic compounds Chemical class 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 230000003137 locomotive effect Effects 0.000 description 1
- 230000006742 locomotor activity Effects 0.000 description 1
- 238000012153 long-term therapy Methods 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000007257 malfunction Effects 0.000 description 1
- 210000005171 mammalian brain Anatomy 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000006984 memory degeneration Effects 0.000 description 1
- 230000003446 memory effect Effects 0.000 description 1
- 208000023060 memory loss Diseases 0.000 description 1
- 230000007595 memory recall Effects 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 238000010197 meta-analysis Methods 0.000 description 1
- 229960001252 methamphetamine Drugs 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 230000001343 mnemonic effect Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000009456 molecular mechanism Effects 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- 230000001095 motoneuron effect Effects 0.000 description 1
- 210000000337 motor cortex Anatomy 0.000 description 1
- 210000002161 motor neuron Anatomy 0.000 description 1
- 206010028093 mucopolysaccharidosis Diseases 0.000 description 1
- 201000002273 mucopolysaccharidosis II Diseases 0.000 description 1
- 208000022018 mucopolysaccharidosis type 2 Diseases 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 230000001338 necrotic effect Effects 0.000 description 1
- 210000001577 neostriatum Anatomy 0.000 description 1
- 210000003061 neural cell Anatomy 0.000 description 1
- 230000003188 neurobehavioral effect Effects 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 230000016273 neuron death Effects 0.000 description 1
- 230000004031 neuronal differentiation Effects 0.000 description 1
- 230000006764 neuronal dysfunction Effects 0.000 description 1
- 230000003961 neuronal insult Effects 0.000 description 1
- 208000002040 neurosyphilis Diseases 0.000 description 1
- 231100000228 neurotoxicity Toxicity 0.000 description 1
- 230000007135 neurotoxicity Effects 0.000 description 1
- 239000002687 nonaqueous vehicle Substances 0.000 description 1
- 239000000346 nonvolatile oil Substances 0.000 description 1
- 201000003077 normal pressure hydrocephalus Diseases 0.000 description 1
- 201000006352 oculocerebrorenal syndrome Diseases 0.000 description 1
- 230000017025 olfactory learning Effects 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 210000002741 palatine tonsil Anatomy 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 238000000554 physical therapy Methods 0.000 description 1
- 238000013439 planning Methods 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 239000008389 polyethoxylated castor oil Substances 0.000 description 1
- 230000004793 poor memory Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 230000008433 psychological processes and functions Effects 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000005067 remediation Methods 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 108020004418 ribosomal RNA Proteins 0.000 description 1
- 210000004761 scalp Anatomy 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000009958 sewing Methods 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 210000004092 somatosensory cortex Anatomy 0.000 description 1
- 238000002630 speech therapy Methods 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 208000003265 stomatitis Diseases 0.000 description 1
- 230000002739 subcortical effect Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 210000001103 thalamus Anatomy 0.000 description 1
- 238000011285 therapeutic regimen Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000005026 transcription initiation Effects 0.000 description 1
- 230000005030 transcription termination Effects 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
- 210000001364 upper extremity Anatomy 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- 210000005172 vertebrate brain Anatomy 0.000 description 1
- 210000000857 visual cortex Anatomy 0.000 description 1
- 235000019156 vitamin B Nutrition 0.000 description 1
- 239000011720 vitamin B Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/4015—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
-
- 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
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4412—Non condensed pyridines; Hydrogenated derivatives thereof having oxo groups directly attached to the heterocyclic ring
-
- 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
- A61P25/18—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
- A61P25/28—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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Epidemiology (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Enzymes And Modification Thereof (AREA)
- Hydrogenated Pyridines (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US80194906P | 2006-05-19 | 2006-05-19 | |
| US60/801.949 | 2006-05-19 | ||
| PCT/US2007/069279 WO2007137181A2 (en) | 2006-05-19 | 2007-05-18 | Phosphodiesterase 4 inhibitors for cognitive and motor rehabilitation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| BRPI0711816A2 true BRPI0711816A2 (pt) | 2011-12-13 |
Family
ID=38617977
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BRPI0711816-3A BRPI0711816A2 (pt) | 2006-05-19 | 2007-05-18 | inibidores fosfodiesterase 4 para rehabilitação motora e cognitiva |
Country Status (11)
| Country | Link |
|---|---|
| EP (2) | EP2377533A3 (cg-RX-API-DMAC10.html) |
| JP (2) | JP2009537568A (cg-RX-API-DMAC10.html) |
| CN (1) | CN101500559B (cg-RX-API-DMAC10.html) |
| AU (1) | AU2007253734B2 (cg-RX-API-DMAC10.html) |
| BR (1) | BRPI0711816A2 (cg-RX-API-DMAC10.html) |
| CA (1) | CA2653042C (cg-RX-API-DMAC10.html) |
| ES (1) | ES2412481T3 (cg-RX-API-DMAC10.html) |
| IL (1) | IL195295A (cg-RX-API-DMAC10.html) |
| MX (1) | MX2008014713A (cg-RX-API-DMAC10.html) |
| SG (2) | SG10201407258RA (cg-RX-API-DMAC10.html) |
| WO (1) | WO2007137181A2 (cg-RX-API-DMAC10.html) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7868015B2 (en) | 2000-08-10 | 2011-01-11 | Cold Spring Harbor Laboratory | Phosphodiesesterase 4 inhibitors for the treatment of a cognitive deficit |
| US7947731B2 (en) | 2000-08-10 | 2011-05-24 | Cold Spring Harbor Laboratory | Augmented cognitive training |
| US9931318B2 (en) | 2003-04-08 | 2018-04-03 | Dart Neuroscience (Cayman) Ltd. | Phosphodiesterase 4 inhibitors for cognitive and motor rehabilitation |
| US8153646B2 (en) | 2000-08-10 | 2012-04-10 | Dart Neuroscience (Cayman) Ltd. | Phosphodiesterase 4 inhibitors for cognitive and motor rehabilitation |
| BRPI0916228A2 (pt) * | 2008-07-18 | 2015-11-03 | Dart Neuroscience Llc | métodos e sistemas para avaliação de agentes de memória |
| WO2011114103A1 (en) | 2010-03-18 | 2011-09-22 | Biolipox Ab | Pyrimidinones for use as medicaments |
| US9727691B2 (en) | 2011-09-30 | 2017-08-08 | Tokyo Metropolitan Institute Of Medical Science | Method for evaluating drug sensitivity and disease vulnerability by analyzing cyclic AMP responsive element binding protein gene |
| US8865723B2 (en) | 2012-10-25 | 2014-10-21 | Tetra Discovery Partners Llc | Selective PDE4 B inhibition and improvement in cognition in subjects with brain injury |
| CA3103781C (en) * | 2019-12-23 | 2023-02-14 | Peter Anthony Hall | Method and system for assessing cognitive function of an individual |
Family Cites Families (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2578001B2 (ja) * | 1989-12-11 | 1997-02-05 | 明治製菓株式会社 | 抗痴呆薬 |
| FI944549L (fi) | 1992-04-02 | 1994-11-30 | Smithkline Beecham Corp | Allergisten ja tulehdussairauksien hoidossa käyttökelpoiset yhdisteet |
| AU678158B2 (en) | 1992-04-10 | 1997-05-22 | Fox Chase Cancer Center | Transcription control element for increasing gene expression in myoblasts |
| JP2001508020A (ja) * | 1994-06-02 | 2001-06-19 | シエーリング アクチエンゲゼルシヤフト | 多発性硬化症治療用のｐｄｅ ｉｖ阻害剤 |
| EP0781335A1 (en) | 1994-10-07 | 1997-07-02 | Cold Spring Harbor Laboratory | Cloning and characterizing of genes associated with long-term memory |
| US5929223A (en) | 1994-10-07 | 1999-07-27 | Cold Spring Harbor Laboratory | Cloning and characterizing of genes associated with long-term memory |
| US5801030A (en) | 1995-09-01 | 1998-09-01 | Genvec, Inc. | Methods and vectors for site-specific recombination |
| WO2000014083A1 (en) | 1998-09-09 | 2000-03-16 | Inflazyme Pharmaceuticals Ltd. | SUBSTITUTED η-PHENYL-Δ-LACTONES AND ANALOGS THEREOF AND USES RELATED THERETO |
| IT1303272B1 (it) | 1998-10-29 | 2000-11-06 | Zambon Spa | Derivati triciclici inibitori della fosfodiesterasi 4 |
| WO2000050402A1 (en) | 1999-02-25 | 2000-08-31 | Merck Frosst Canada & Co. | Pde iv inhibiting compounds, compositions and methods of treatment |
| US6436965B1 (en) | 2000-03-02 | 2002-08-20 | Merck Frosst Canada & Co. | PDE IV inhibiting amides, compositions and methods of treatment |
| CA2402384A1 (en) | 2000-03-16 | 2001-09-20 | Inflazyme Pharmaceuticals Ltd. | Benzylated pde4 inhibitors |
| US7947731B2 (en) * | 2000-08-10 | 2011-05-24 | Cold Spring Harbor Laboratory | Augmented cognitive training |
| US20040224316A1 (en) * | 2000-08-10 | 2004-11-11 | Tully Timothy P. | Augmented cognitive training |
| JP2004532809A (ja) * | 2000-11-02 | 2004-10-28 | リサーチ ファウンデーション オブ シティ ユニバーシティ オブ ニューヨーク | ホスホジエステラーゼ４型を阻害することによって、神経系の再生および修復を刺激するための方法 |
| WO2003032981A1 (en) * | 2001-10-16 | 2003-04-24 | Memory Pharmaceuticals Corporation | 4-(4-alkoxy-3-hydroxyphenyl)-2-pyrrolidone derivatives as pde-4 inhibitors for the treatment of neurological syndromes |
| AU2003210869A1 (en) * | 2002-02-07 | 2003-09-02 | University Of Miami | Schwann cell and phosphodiesterase inhibitors based therapy |
| WO2004082624A2 (en) * | 2003-03-17 | 2004-09-30 | Neurohealing Pharmaceuticals, Inc. | Modafinil-based neurorehabilitation of impaired neurological function associated with injury |
| US20090298864A1 (en) * | 2005-04-11 | 2009-12-03 | The Trustees Of Columbia University In The City Of New York | Methods for Treating Mild Cognitive Impairment |
-
2007
- 2007-05-18 EP EP11158676A patent/EP2377533A3/en not_active Withdrawn
- 2007-05-18 AU AU2007253734A patent/AU2007253734B2/en not_active Ceased
- 2007-05-18 SG SG10201407258RA patent/SG10201407258RA/en unknown
- 2007-05-18 ES ES07783945T patent/ES2412481T3/es active Active
- 2007-05-18 MX MX2008014713A patent/MX2008014713A/es active IP Right Grant
- 2007-05-18 WO PCT/US2007/069279 patent/WO2007137181A2/en not_active Ceased
- 2007-05-18 BR BRPI0711816-3A patent/BRPI0711816A2/pt not_active IP Right Cessation
- 2007-05-18 JP JP2009511250A patent/JP2009537568A/ja active Pending
- 2007-05-18 EP EP07783945A patent/EP2021001B1/en not_active Not-in-force
- 2007-05-18 SG SG2011035813A patent/SG172602A1/en unknown
- 2007-05-18 CN CN200780026381.9A patent/CN101500559B/zh not_active Expired - Fee Related
- 2007-05-18 CA CA2653042A patent/CA2653042C/en not_active Expired - Fee Related
-
2008
- 2008-11-13 IL IL195295A patent/IL195295A/en active IP Right Grant
-
2014
- 2014-10-30 JP JP2014220896A patent/JP2015042667A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| WO2007137181A2 (en) | 2007-11-29 |
| SG172602A1 (en) | 2011-07-28 |
| EP2021001B1 (en) | 2012-12-12 |
| CA2653042C (en) | 2016-07-05 |
| CN101500559A (zh) | 2009-08-05 |
| IL195295A (en) | 2015-11-30 |
| ES2412481T3 (es) | 2013-07-11 |
| EP2021001A2 (en) | 2009-02-11 |
| AU2007253734B2 (en) | 2013-07-25 |
| MX2008014713A (es) | 2009-04-17 |
| HK1130656A1 (en) | 2010-01-08 |
| SG10201407258RA (en) | 2015-01-29 |
| EP2377533A3 (en) | 2012-02-22 |
| CA2653042A1 (en) | 2007-11-29 |
| JP2015042667A (ja) | 2015-03-05 |
| EP2377533A2 (en) | 2011-10-19 |
| CN101500559B (zh) | 2014-01-08 |
| WO2007137181A3 (en) | 2008-08-07 |
| AU2007253734A1 (en) | 2007-11-29 |
| JP2009537568A (ja) | 2009-10-29 |
| IL195295A0 (en) | 2009-08-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2373540T3 (es) | Entrenamiento cognitivo aumentado. | |
| US9931318B2 (en) | Phosphodiesterase 4 inhibitors for cognitive and motor rehabilitation | |
| US10188640B2 (en) | Phosphodiesesterase 4 inhibitors for the treatment of a cognitive deficit | |
| JP2015042667A (ja) | 認知および運動のリハビリテーションのためのホスホジエステラーゼ４インヒビター | |
| ES2403333T3 (es) | Entrenamiento cognitivo aumentado | |
| Talifu et al. | The overexpression of insulin-like growth factor-1 and neurotrophin-3 promote functional recovery and alleviate spasticity after spinal cord injury | |
| US9795591B2 (en) | Phosphodiesterase 4 inhibitors for cognitive and motor rehabilitation | |
| Belaya | Exercise-induced cellular and molecular alterations in aging and Alzheimer’s disease | |
| HK1130656B (en) | Phosphodiesterase 4 inhibitors for motor rehabilitation | |
| KR20110049801A (ko) | 기억 물질의 평가를 위한 방법 및 시스템 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| B07D | Technical examination (opinion) related to article 229 of industrial property law [chapter 7.4 patent gazette] | ||
| B06F | Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette] | ||
| B08F | Application dismissed because of non-payment of annual fees [chapter 8.6 patent gazette] |
Free format text: REFERENTE A 12A ANUIDADE. |
|
| B08K | Patent lapsed as no evidence of payment of the annual fee has been furnished to inpi [chapter 8.11 patent gazette] |
Free format text: EM VIRTUDE DO ARQUIVAMENTO PUBLICADO NA RPI 2516 DE 26-03-2019 E CONSIDERANDO AUSENCIA DE MANIFESTACAO DENTRO DOS PRAZOS LEGAIS, INFORMO QUE CABE SER MANTIDO O ARQUIVAMENTO DO PEDIDO DE PATENTE, CONFORME O DISPOSTO NO ARTIGO 12, DA RESOLUCAO 113/2013. |