WO2000003701A1 - Composition for treatment of stress - Google Patents
Composition for treatment of stress Download PDFInfo
- Publication number
- WO2000003701A1 WO2000003701A1 PCT/US1999/016153 US9916153W WO0003701A1 WO 2000003701 A1 WO2000003701 A1 WO 2000003701A1 US 9916153 W US9916153 W US 9916153W WO 0003701 A1 WO0003701 A1 WO 0003701A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- pharmaceutically acceptable
- acceptable salt
- day
- administered
- effective amount
- Prior art date
Links
- 238000011282 treatment Methods 0.000 title description 66
- 239000000203 mixture Substances 0.000 title description 9
- 238000000034 method Methods 0.000 claims abstract description 53
- 150000003839 salts Chemical class 0.000 claims abstract description 50
- DBGIVFWFUFKIQN-VIFPVBQESA-N (+)-Fenfluramine Chemical compound CCN[C@@H](C)CC1=CC=CC(C(F)(F)F)=C1 DBGIVFWFUFKIQN-VIFPVBQESA-N 0.000 claims abstract description 44
- 229960004597 dexfenfluramine Drugs 0.000 claims abstract description 44
- XJJZQXUGLLXTHO-ZETCQYMHSA-N (2S)-1-(6-chloro-5-fluoroindol-1-yl)-propan-2-amine Chemical compound FC1=C(Cl)C=C2N(C[C@@H](N)C)C=CC2=C1 XJJZQXUGLLXTHO-ZETCQYMHSA-N 0.000 claims abstract description 27
- 208000024891 symptom Diseases 0.000 claims abstract description 20
- CJAWPFJGFFNXQI-UHFFFAOYSA-N 2-chloro-6-(1-piperazinyl)pyrazine Chemical compound ClC1=CN=CC(N2CCNCC2)=N1 CJAWPFJGFFNXQI-UHFFFAOYSA-N 0.000 claims abstract description 19
- SACMXZDUZMBKSI-GYDOPSIJSA-N (e)-but-2-enedioic acid;(2s)-1-(4,4,7-trimethylindeno[1,2-b]pyrrol-1-yl)propan-2-amine Chemical compound OC(=O)\C=C\C(O)=O.C12=CC(C)=CC=C2C(C)(C)C2=C1N(C[C@@H](N)C)C=C2 SACMXZDUZMBKSI-GYDOPSIJSA-N 0.000 claims abstract description 15
- 229960002073 sertraline Drugs 0.000 claims abstract description 8
- VGKDLMBJGBXTGI-SJCJKPOMSA-N sertraline Chemical compound C1([C@@H]2CC[C@@H](C3=CC=CC=C32)NC)=CC=C(Cl)C(Cl)=C1 VGKDLMBJGBXTGI-SJCJKPOMSA-N 0.000 claims abstract description 8
- RTHCYVBBDHJXIQ-MRXNPFEDSA-N (R)-fluoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-MRXNPFEDSA-N 0.000 claims abstract description 7
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims abstract description 7
- 229960002464 fluoxetine Drugs 0.000 claims abstract description 7
- 229910052744 lithium Inorganic materials 0.000 claims abstract description 7
- 229960004038 fluvoxamine Drugs 0.000 claims abstract description 6
- CJOFXWAVKWHTFT-XSFVSMFZSA-N fluvoxamine Chemical compound COCCCC\C(=N/OCCN)C1=CC=C(C(F)(F)F)C=C1 CJOFXWAVKWHTFT-XSFVSMFZSA-N 0.000 claims abstract description 6
- GDLIGKIOYRNHDA-UHFFFAOYSA-N Clomipramine Chemical compound C1CC2=CC=C(Cl)C=C2N(CCCN(C)C)C2=CC=CC=C21 GDLIGKIOYRNHDA-UHFFFAOYSA-N 0.000 claims abstract description 4
- 229960004606 clomipramine Drugs 0.000 claims abstract description 4
- 229960001078 lithium Drugs 0.000 claims abstract description 4
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 claims description 38
- 150000001875 compounds Chemical class 0.000 claims description 22
- -1 cyanimipramine Chemical compound 0.000 claims description 20
- 229940076279 serotonin Drugs 0.000 claims description 19
- DBGIVFWFUFKIQN-SECBINFHSA-N Levofenfluramine Chemical compound CCN[C@H](C)CC1=CC=CC(C(F)(F)F)=C1 DBGIVFWFUFKIQN-SECBINFHSA-N 0.000 claims description 16
- 230000001404 mediated effect Effects 0.000 claims description 15
- 230000005062 synaptic transmission Effects 0.000 claims description 15
- 230000037396 body weight Effects 0.000 claims description 14
- BYTRZQOWWRJDMZ-ZETCQYMHSA-N (2s)-1-(2-chloro-5-fluoroindol-1-yl)propan-2-amine Chemical compound FC1=CC=C2N(C[C@@H](N)C)C(Cl)=CC2=C1 BYTRZQOWWRJDMZ-ZETCQYMHSA-N 0.000 claims description 8
- 230000001242 postsynaptic effect Effects 0.000 claims description 8
- 230000001747 exhibiting effect Effects 0.000 claims description 7
- VHFVKMTVMIZMIK-UHFFFAOYSA-N 1-(3-chlorophenyl)piperazine Chemical compound ClC1=CC=CC(N2CCNCC2)=C1 VHFVKMTVMIZMIK-UHFFFAOYSA-N 0.000 claims description 6
- 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 claims description 6
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 claims description 6
- RMUCZJUITONUFY-UHFFFAOYSA-N Phenelzine Chemical compound NNCCC1=CC=CC=C1 RMUCZJUITONUFY-UHFFFAOYSA-N 0.000 claims description 6
- VTTONGPRPXSUTJ-UHFFFAOYSA-N bufotenin Chemical compound C1=C(O)C=C2C(CCN(C)C)=CNC2=C1 VTTONGPRPXSUTJ-UHFFFAOYSA-N 0.000 claims description 6
- 229960004801 imipramine Drugs 0.000 claims description 6
- BCGWQEUPMDMJNV-UHFFFAOYSA-N imipramine Chemical compound C1CC2=CC=CC=C2N(CCCN(C)C)C2=CC=CC=C21 BCGWQEUPMDMJNV-UHFFFAOYSA-N 0.000 claims description 6
- SADQVAVFGNTEOD-UHFFFAOYSA-N indalpine Chemical compound C=1NC2=CC=CC=C2C=1CCC1CCNCC1 SADQVAVFGNTEOD-UHFFFAOYSA-N 0.000 claims description 6
- QZYYPQAYSFBKPW-UHFFFAOYSA-N org 12962 Chemical compound N1=C(Cl)C(C(F)(F)F)=CC=C1N1CCNCC1 QZYYPQAYSFBKPW-UHFFFAOYSA-N 0.000 claims description 6
- 229960000964 phenelzine Drugs 0.000 claims description 6
- 229960002431 trimipramine Drugs 0.000 claims description 6
- ZSCDBOWYZJWBIY-UHFFFAOYSA-N trimipramine Chemical compound C1CC2=CC=CC=C2N(CC(CN(C)C)C)C2=CC=CC=C21 ZSCDBOWYZJWBIY-UHFFFAOYSA-N 0.000 claims description 6
- PNVNVHUZROJLTJ-UHFFFAOYSA-N venlafaxine Chemical compound C1=CC(OC)=CC=C1C(CN(C)C)C1(O)CCCCC1 PNVNVHUZROJLTJ-UHFFFAOYSA-N 0.000 claims description 6
- 229960000836 amitriptyline Drugs 0.000 claims description 5
- KRMDCWKBEZIMAB-UHFFFAOYSA-N amitriptyline Chemical compound C1CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21 KRMDCWKBEZIMAB-UHFFFAOYSA-N 0.000 claims description 5
- 229960003991 trazodone Drugs 0.000 claims description 5
- PHLBKPHSAVXXEF-UHFFFAOYSA-N trazodone Chemical compound ClC1=CC=CC(N2CCN(CCCN3C(N4C=CC=CC4=N3)=O)CC2)=C1 PHLBKPHSAVXXEF-UHFFFAOYSA-N 0.000 claims description 5
- 229960004688 venlafaxine Drugs 0.000 claims description 5
- AHOUBRCZNHFOSL-YOEHRIQHSA-N (+)-Casbol Chemical compound C1=CC(F)=CC=C1[C@H]1[C@H](COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-YOEHRIQHSA-N 0.000 claims description 4
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 claims description 4
- AHOUBRCZNHFOSL-UHFFFAOYSA-N Paroxetine hydrochloride Natural products C1=CC(F)=CC=C1C1C(COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-UHFFFAOYSA-N 0.000 claims description 4
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 claims description 4
- SNPPWIUOZRMYNY-UHFFFAOYSA-N bupropion Chemical compound CC(C)(C)NC(C)C(=O)C1=CC=CC(Cl)=C1 SNPPWIUOZRMYNY-UHFFFAOYSA-N 0.000 claims description 4
- 229960001058 bupropion Drugs 0.000 claims description 4
- VRBKIVRKKCLPHA-UHFFFAOYSA-N nefazodone Chemical compound O=C1N(CCOC=2C=CC=CC=2)C(CC)=NN1CCCN(CC1)CCN1C1=CC=CC(Cl)=C1 VRBKIVRKKCLPHA-UHFFFAOYSA-N 0.000 claims description 4
- 229960001800 nefazodone Drugs 0.000 claims description 4
- 229960002296 paroxetine Drugs 0.000 claims description 4
- 229960004799 tryptophan Drugs 0.000 claims description 4
- IGLYMJRIWWIQQE-QUOODJBBSA-N (1S,2R)-2-phenylcyclopropan-1-amine (1R,2S)-2-phenylcyclopropan-1-amine Chemical compound N[C@H]1C[C@@H]1C1=CC=CC=C1.N[C@@H]1C[C@H]1C1=CC=CC=C1 IGLYMJRIWWIQQE-QUOODJBBSA-N 0.000 claims description 3
- ASNYPHGOFQAGQM-VQIMIIECSA-N (5r,7r)-n,n-dimethyl-5-(4-nitrophenoxy)-6,7,8,9-tetrahydro-5h-benzo[7]annulen-7-amine Chemical compound O([C@H]1C2=CC=CC=C2CC[C@H](C1)N(C)C)C1=CC=C([N+]([O-])=O)C=C1 ASNYPHGOFQAGQM-VQIMIIECSA-N 0.000 claims description 3
- OWOHLURDBZHNGG-YFKPBYRVSA-N (8ar)-hexahydropyrrolo[1,2-a]pyrazine-1,4-dione Chemical compound O=C1CNC(=O)[C@@H]2CCCN12 OWOHLURDBZHNGG-YFKPBYRVSA-N 0.000 claims description 3
- WSEQXVZVJXJVFP-HXUWFJFHSA-N (R)-citalopram Chemical compound C1([C@@]2(C3=CC=C(C=C3CO2)C#N)CCCN(C)C)=CC=C(F)C=C1 WSEQXVZVJXJVFP-HXUWFJFHSA-N 0.000 claims description 3
- LXOHMGALVZOYRF-BTJKTKAUSA-N (z)-but-2-enedioic acid;6-nitro-2-piperazin-1-ylquinoline Chemical compound OC(=O)\C=C/C(O)=O.C1=CC2=CC([N+](=O)[O-])=CC=C2N=C1N1CCNCC1 LXOHMGALVZOYRF-BTJKTKAUSA-N 0.000 claims description 3
- KKIMDKMETPPURN-UHFFFAOYSA-N 1-(3-(trifluoromethyl)phenyl)piperazine Chemical compound FC(F)(F)C1=CC=CC(N2CCNCC2)=C1 KKIMDKMETPPURN-UHFFFAOYSA-N 0.000 claims description 3
- LXFHSCDLMBZYKY-UHFFFAOYSA-N 4-(4-methylpiperazin-1-yl)-7-(trifluoromethyl)pyrrolo[1,2-a]quinoxaline Chemical compound C1CN(C)CCN1C1=NC2=CC(C(F)(F)F)=CC=C2N2C1=CC=C2 LXFHSCDLMBZYKY-UHFFFAOYSA-N 0.000 claims description 3
- WKZLNEWVIAGNAW-UHFFFAOYSA-N 5-Carboxyamidotryptamine Chemical compound C1=C(C(N)=O)C=C2C(CCN)=CNC2=C1 WKZLNEWVIAGNAW-UHFFFAOYSA-N 0.000 claims description 3
- XKFPYPQQHFEXRZ-UHFFFAOYSA-N 5-methyl-N'-(phenylmethyl)-3-isoxazolecarbohydrazide Chemical compound O1C(C)=CC(C(=O)NNCC=2C=CC=CC=2)=N1 XKFPYPQQHFEXRZ-UHFFFAOYSA-N 0.000 claims description 3
- ASXGJMSKWNBENU-UHFFFAOYSA-N 8-OH-DPAT Chemical compound C1=CC(O)=C2CC(N(CCC)CCC)CCC2=C1 ASXGJMSKWNBENU-UHFFFAOYSA-N 0.000 claims description 3
- PHVGLTMQBUFIQQ-UHFFFAOYSA-N Nortryptiline Chemical compound C1CC2=CC=CC=C2C(=CCCNC)C2=CC=CC=C21 PHVGLTMQBUFIQQ-UHFFFAOYSA-N 0.000 claims description 3
- RVSGRNKUJJUAPV-UHFFFAOYSA-N benzo[d][1,2]benzoxazepine Chemical compound O1N=CC2=CC=CC=C2C2=CC=CC=C12 RVSGRNKUJJUAPV-UHFFFAOYSA-N 0.000 claims description 3
- 229950001408 cianopramine Drugs 0.000 claims description 3
- LQXYCDLHSKICDY-UHFFFAOYSA-N cianopramine Chemical compound C1CC2=CC=C(C#N)C=C2N(CCCN(C)C)C2=CC=CC=C21 LQXYCDLHSKICDY-UHFFFAOYSA-N 0.000 claims description 3
- 229960001653 citalopram Drugs 0.000 claims description 3
- 229960005426 doxepin Drugs 0.000 claims description 3
- ODQWQRRAPPTVAG-GZTJUZNOSA-N doxepin Chemical compound C1OC2=CC=CC=C2C(=C/CCN(C)C)/C2=CC=CC=C21 ODQWQRRAPPTVAG-GZTJUZNOSA-N 0.000 claims description 3
- 229960001625 furazolidone Drugs 0.000 claims description 3
- PLHJDBGFXBMTGZ-WEVVVXLNSA-N furazolidone Chemical compound O1C([N+](=O)[O-])=CC=C1\C=N\N1C(=O)OCC1 PLHJDBGFXBMTGZ-WEVVVXLNSA-N 0.000 claims description 3
- 229950002473 indalpine Drugs 0.000 claims description 3
- 229960002672 isocarboxazid Drugs 0.000 claims description 3
- YHXISWVBGDMDLQ-UHFFFAOYSA-N moclobemide Chemical compound C1=CC(Cl)=CC=C1C(=O)NCCN1CCOCC1 YHXISWVBGDMDLQ-UHFFFAOYSA-N 0.000 claims description 3
- 229960004644 moclobemide Drugs 0.000 claims description 3
- 229960001158 nortriptyline Drugs 0.000 claims description 3
- LWRJZIPAGMGXQJ-DIJVWCDGSA-N org-6582 Chemical compound Cl.C1C2=CC(Cl)=CC=C2[C@@H]2[C@@H](N)[C@H]1C=CC2 LWRJZIPAGMGXQJ-DIJVWCDGSA-N 0.000 claims description 3
- CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 claims description 3
- 229960000624 procarbazine Drugs 0.000 claims description 3
- 229960002601 protriptyline Drugs 0.000 claims description 3
- BWPIARFWQZKAIA-UHFFFAOYSA-N protriptyline Chemical compound C1=CC2=CC=CC=C2C(CCCNC)C2=CC=CC=C21 BWPIARFWQZKAIA-UHFFFAOYSA-N 0.000 claims description 3
- XRXDAJYKGWNHTQ-UHFFFAOYSA-N quipazine Chemical compound C1CNCCN1C1=CC=C(C=CC=C2)C2=N1 XRXDAJYKGWNHTQ-UHFFFAOYSA-N 0.000 claims description 3
- 229950002315 quipazine Drugs 0.000 claims description 3
- MEZLKOACVSPNER-GFCCVEGCSA-N selegiline Chemical compound C#CCN(C)[C@H](C)CC1=CC=CC=C1 MEZLKOACVSPNER-GFCCVEGCSA-N 0.000 claims description 3
- 229960004425 sibutramine Drugs 0.000 claims description 3
- UNAANXDKBXWMLN-UHFFFAOYSA-N sibutramine Chemical compound C=1C=C(Cl)C=CC=1C1(C(N(C)C)CC(C)C)CCC1 UNAANXDKBXWMLN-UHFFFAOYSA-N 0.000 claims description 3
- KQKPFRSPSRPDEB-UHFFFAOYSA-N sumatriptan Chemical compound CNS(=O)(=O)CC1=CC=C2NC=C(CCN(C)C)C2=C1 KQKPFRSPSRPDEB-UHFFFAOYSA-N 0.000 claims description 3
- 229960003708 sumatriptan Drugs 0.000 claims description 3
- 229960003741 tranylcypromine Drugs 0.000 claims description 3
- 229960002791 zimeldine Drugs 0.000 claims description 3
- OYPPVKRFBIWMSX-SXGWCWSVSA-N zimeldine Chemical compound C=1C=CN=CC=1C(=C/CN(C)C)\C1=CC=C(Br)C=C1 OYPPVKRFBIWMSX-SXGWCWSVSA-N 0.000 claims description 3
- LIWAQLJGPBVORC-UHFFFAOYSA-N N-ethyl-N-methylamine Natural products CCNC LIWAQLJGPBVORC-UHFFFAOYSA-N 0.000 claims description 2
- WZXHSWVDAYOFPE-UHFFFAOYSA-N brofaromine Chemical compound C=1C2=CC(OC)=CC(Br)=C2OC=1C1CCNCC1 WZXHSWVDAYOFPE-UHFFFAOYSA-N 0.000 claims description 2
- 229950004068 brofaromine Drugs 0.000 claims description 2
- IPIHGDDHIVDPOJ-LBPRGKRZSA-N (2s)-1-(4,4,7-trimethylindeno[1,2-b]pyrrol-1-yl)propan-2-amine Chemical compound C12=CC(C)=CC=C2C(C)(C)C2=C1N(C[C@@H](N)C)C=C2 IPIHGDDHIVDPOJ-LBPRGKRZSA-N 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 39
- 229940079593 drug Drugs 0.000 abstract description 37
- 230000002295 serotoninergic effect Effects 0.000 abstract description 14
- 230000035882 stress Effects 0.000 description 92
- 235000005686 eating Nutrition 0.000 description 27
- 241000700159 Rattus Species 0.000 description 18
- 230000002996 emotional effect Effects 0.000 description 16
- 230000007423 decrease Effects 0.000 description 15
- 230000000694 effects Effects 0.000 description 15
- 206010020710 Hyperphagia Diseases 0.000 description 13
- 235000020830 overeating Nutrition 0.000 description 13
- 235000013305 food Nutrition 0.000 description 12
- 206010049119 Emotional distress Diseases 0.000 description 9
- 208000008589 Obesity Diseases 0.000 description 9
- 235000020824 obesity Nutrition 0.000 description 9
- 241000282412 Homo Species 0.000 description 7
- 230000036528 appetite Effects 0.000 description 7
- 235000019789 appetite Nutrition 0.000 description 7
- DBGIVFWFUFKIQN-UHFFFAOYSA-N (+-)-Fenfluramine Chemical compound CCNC(C)CC1=CC=CC(C(F)(F)F)=C1 DBGIVFWFUFKIQN-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 230000006399 behavior Effects 0.000 description 6
- 230000020595 eating behavior Effects 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- 206010033307 Overweight Diseases 0.000 description 5
- 235000019788 craving Nutrition 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 229960001582 fenfluramine Drugs 0.000 description 5
- 230000037406 food intake Effects 0.000 description 5
- 235000012631 food intake Nutrition 0.000 description 5
- 235000012054 meals Nutrition 0.000 description 5
- 239000008194 pharmaceutical composition Substances 0.000 description 5
- 238000011160 research Methods 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 208000016261 weight loss Diseases 0.000 description 5
- 230000004580 weight loss Effects 0.000 description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- 210000004556 brain Anatomy 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 208000035475 disorder Diseases 0.000 description 4
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 4
- 238000012216 screening Methods 0.000 description 4
- 235000011888 snacks Nutrition 0.000 description 4
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 4
- 208000019901 Anxiety disease Diseases 0.000 description 3
- 206010056465 Food craving Diseases 0.000 description 3
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 3
- 230000036506 anxiety Effects 0.000 description 3
- 239000002249 anxiolytic agent Substances 0.000 description 3
- 230000000949 anxiolytic effect Effects 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 235000009508 confectionery Nutrition 0.000 description 3
- 235000005911 diet Nutrition 0.000 description 3
- 230000037213 diet Effects 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 230000008451 emotion Effects 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 235000003642 hunger Nutrition 0.000 description 3
- 230000000977 initiatory effect Effects 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 239000005711 Benzoic acid Substances 0.000 description 2
- 206010048909 Boredom Diseases 0.000 description 2
- GIYXAJPCNFJEHY-UHFFFAOYSA-N N-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]-1-propanamine hydrochloride (1:1) Chemical compound Cl.C=1C=CC=CC=1C(CCNC)OC1=CC=C(C(F)(F)F)C=C1 GIYXAJPCNFJEHY-UHFFFAOYSA-N 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 2
- 241000482268 Zea mays subsp. mays Species 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- LYPCGXKCQDYTFV-UHFFFAOYSA-N alpha-methylserotonin Chemical compound C1=C(O)C=C2C(CC(N)C)=CNC2=C1 LYPCGXKCQDYTFV-UHFFFAOYSA-N 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000002180 anti-stress Effects 0.000 description 2
- 229940005530 anxiolytics Drugs 0.000 description 2
- 229940049706 benzodiazepine Drugs 0.000 description 2
- 150000001557 benzodiazepines Chemical class 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- 239000002876 beta blocker Substances 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000019219 chocolate Nutrition 0.000 description 2
- 229960000389 fluoxetine hydrochloride Drugs 0.000 description 2
- 230000035929 gnawing Effects 0.000 description 2
- 235000015243 ice cream Nutrition 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000003278 mimic effect Effects 0.000 description 2
- 230000036651 mood Effects 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 229960003712 propranolol Drugs 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 229940005605 valeric acid Drugs 0.000 description 2
- 239000013585 weight reducing agent Substances 0.000 description 2
- ZXKXJHAOUFHNAS-FVGYRXGTSA-N (S)-fenfluramine hydrochloride Chemical compound [Cl-].CC[NH2+][C@@H](C)CC1=CC=CC(C(F)(F)F)=C1 ZXKXJHAOUFHNAS-FVGYRXGTSA-N 0.000 description 1
- GLQPTZAAUROJMO-UHFFFAOYSA-N 4-(3,4-dimethoxyphenyl)benzaldehyde Chemical compound C1=C(OC)C(OC)=CC=C1C1=CC=C(C=O)C=C1 GLQPTZAAUROJMO-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- KFYRPLNVJVHZGT-UHFFFAOYSA-N Amitriptyline hydrochloride Chemical compound Cl.C1CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21 KFYRPLNVJVHZGT-UHFFFAOYSA-N 0.000 description 1
- 244000105624 Arachis hypogaea Species 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 206010004716 Binge eating Diseases 0.000 description 1
- 208000032841 Bulimia Diseases 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- PTHCMJGKKRQCBF-UHFFFAOYSA-N Cellulose, microcrystalline Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC)C(CO)O1 PTHCMJGKKRQCBF-UHFFFAOYSA-N 0.000 description 1
- 241000238557 Decapoda Species 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- LFMYNZPAVPMEGP-PIDGMYBPSA-N Fluvoxamine maleate Chemical compound OC(=O)\C=C/C(O)=O.COCCCC\C(=N/OCCN)C1=CC=C(C(F)(F)F)C=C1 LFMYNZPAVPMEGP-PIDGMYBPSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 229920000084 Gum arabic Polymers 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
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- RXBKMJIPNDOHFR-UHFFFAOYSA-N Phenelzine sulfate Chemical compound OS(O)(=O)=O.NNCCC1=CC=CC=C1 RXBKMJIPNDOHFR-UHFFFAOYSA-N 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- 206010042209 Stress Diseases 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 229960005119 amitriptyline hydrochloride Drugs 0.000 description 1
- 229940125709 anorectic agent Drugs 0.000 description 1
- 230000001539 anorectic effect Effects 0.000 description 1
- 239000002830 appetite depressant Substances 0.000 description 1
- 235000015173 baked goods and baking mixes Nutrition 0.000 description 1
- 235000013405 beer Nutrition 0.000 description 1
- 229940097320 beta blocking agent Drugs 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 208000014679 binge eating disease Diseases 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 235000008429 bread Nutrition 0.000 description 1
- 235000014121 butter Nutrition 0.000 description 1
- 235000012970 cakes Nutrition 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 235000010675 chips/crisps Nutrition 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 235000014510 cooky Nutrition 0.000 description 1
- 235000012495 crackers Nutrition 0.000 description 1
- 229960001096 dexfenfluramine hydrochloride Drugs 0.000 description 1
- 229960003529 diazepam Drugs 0.000 description 1
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 235000006694 eating habits Nutrition 0.000 description 1
- 229940098766 effexor Drugs 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000001667 episodic effect Effects 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 229960004667 ethyl cellulose Drugs 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 229960002107 fluvoxamine maleate Drugs 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- XZZXIYZZBJDEEP-UHFFFAOYSA-N imipramine hydrochloride Chemical compound [Cl-].C1CC2=CC=CC=C2N(CCC[NH+](C)C)C2=CC=CC=C21 XZZXIYZZBJDEEP-UHFFFAOYSA-N 0.000 description 1
- 229960002102 imipramine hydrochloride Drugs 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 description 1
- 229910052808 lithium carbonate Inorganic materials 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- GVALZJMUIHGIMD-UHFFFAOYSA-H magnesium phosphate Chemical compound [Mg+2].[Mg+2].[Mg+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O GVALZJMUIHGIMD-UHFFFAOYSA-H 0.000 description 1
- 239000004137 magnesium phosphate Substances 0.000 description 1
- 229960002261 magnesium phosphate Drugs 0.000 description 1
- 229910000157 magnesium phosphate Inorganic materials 0.000 description 1
- 235000010994 magnesium phosphates Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000037323 metabolic rate Effects 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- CGBNQBFFXDURAY-UHFFFAOYSA-N n-propan-2-ylpyrrol-1-amine Chemical compound CC(C)NN1C=CC=C1 CGBNQBFFXDURAY-UHFFFAOYSA-N 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 235000020232 peanut Nutrition 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229960004790 phenelzine sulfate Drugs 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 235000013606 potato chips Nutrition 0.000 description 1
- 235000012015 potatoes Nutrition 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 235000012434 pretzels Nutrition 0.000 description 1
- 230000003938 response to stress Effects 0.000 description 1
- 230000036186 satiety Effects 0.000 description 1
- 235000019627 satiety Nutrition 0.000 description 1
- 229960003660 sertraline hydrochloride Drugs 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 230000004037 social stress Effects 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 239000006190 sub-lingual tablet Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 235000021147 sweet food Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229960002301 trazodone hydrochloride Drugs 0.000 description 1
- OHHDIOKRWWOXMT-UHFFFAOYSA-N trazodone hydrochloride Chemical compound [H+].[Cl-].ClC1=CC=CC(N2CCN(CCCN3C(N4C=CC=CC4=N3)=O)CC2)=C1 OHHDIOKRWWOXMT-UHFFFAOYSA-N 0.000 description 1
- 229960002835 trimipramine maleate Drugs 0.000 description 1
- YDGHCKHAXOUQOS-BTJKTKAUSA-N trimipramine maleate Chemical compound [O-]C(=O)\C=C/C([O-])=O.C1CC2=CC=CC=C2[NH+](CC(C[NH+](C)C)C)C2=CC=CC=C21 YDGHCKHAXOUQOS-BTJKTKAUSA-N 0.000 description 1
- 229960002416 venlafaxine hydrochloride Drugs 0.000 description 1
- QYRYFNHXARDNFZ-UHFFFAOYSA-N venlafaxine hydrochloride Chemical compound [H+].[Cl-].C1=CC(OC)=CC=C1C(CN(C)C)C1(O)CCCCC1 QYRYFNHXARDNFZ-UHFFFAOYSA-N 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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
-
- 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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
-
- 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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/138—Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
-
- 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
- A61K31/13—Amines
- A61K31/15—Oximes (>C=N—O—); Hydrazines (>N—N<); Hydrazones (>N—N=) ; Imines (C—N=C)
-
- 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
- A61K31/403—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 condensed with carbocyclic rings, e.g. carbazole
-
- 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
- A61K31/403—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 condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
- A61K31/4045—Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Definitions
- the invention relates to a novel process for treating stress in a subject suffering from at least one symptom of stress. More specifically, the invention relates to the use of drugs which enhance serotonin-mediated neurotransmission such as fenfluramines for treating stress in such a subject.
- a patient suffering from a stress related disorder may exhibit a variety of types of symptoms. These symptoms can include anxiety, depression, and overeating.
- the conventional treatment for a patient suffering from a stress related disorder is by use of drugs such as the benzodiazepines or by use of beta- blocking drugs such as propranolol.
- Disclosed here is a novel treatment method for stress in a patient, which method uses drugs hitherto unknown as useful for treating stress.
- the novel method disclosed herein provides a useful method for treating patients suffering from stress and exhibiting at least one symptom thereof. In a specific embodiment of the invention, said method has been found particularly useful for treating the stress felt by subjects who also suffer from overeating disorders or who overeat in reaction to the stress that they are experiencing.
- a number of compounds are known to stimulate or enhance serotonin-mediated neurotransmission and are sometimes referred to as serotoninergic drugs. These compounds include the following: d,l-fenfiurarnine, dexfenfluramine, tryptophan, lithium, chlorimipramine, cyanimipramine, fluoxetine, paroxetine, fluvoxamine, citalopram, femoxitine, cianopramine, sertraline, sibutramine, venlafaxine, ORG 6582, RU 25591, LM 5008, DU 24565, indalpine, CGP 6085/A, W ⁇ 25093, alaprociate, zimelidine, trazodone, amitriptyline, imipramine, trimipramine, doxepin, protriptyline, nortriptyline, dibenzoxazepine, deprenyl, isocarboxazide, phenelzine, tranylcypromine,
- Suitable salts can be formed from the above compounds, for example, as addition salts using the following acids: the hydrohalic acids, sulfuric acid, phosphoric acid or an organic acid such as acetic acid, maleic acid, valeric acid, caproic acid, benzoic acid or nicotine acid.
- fenfluramines here is meant a racemic mixture of d,l-fenfluramine, which is also called N-ethyl- ⁇ -methyl-3-(trifluoro-methyl)benzeneethanamine; the dextrorotatory isomer known as dexfenflurarnine and also as d-fenfluramine; or the pharmaceutically acceptable salts of these compounds.
- Suitable salts can be formed from dexfenflurarnine or d,l-fenfluramine, for example, as addition salts using the following acids: the hydrohalic acids, sulfuric acid, phosphoric acid or an organic acid such as acetic acid, maleic acid, valeric acid, caproic acid, benzoic acid or nicotinic acid.
- the active serotonin-mediated neurotransmission stimulating compound may be administered to a patient as a pharmaceutical composition comprising the active compound admixed with a pharmaceutically acceptable carrier, including one or more excipients.
- fenfluramines may be administered to a patient as a pharmaceutical composition comprising either dexfenflurarnine or d,l-fenfluramine admixed with a pharmaceutically acceptable carrier, including one or more excipients.
- the terms “subject” and “patient” may be used interchangeably to refer to a human exhibiting at least one symptom of stress.
- compositions of this invention are suitable for parenteral, buccal, sublingual or rectal administration.
- the resulting pharmaceutical compositions are, for example, tablets, coated tablets, capsules, soft gelatin capsules, drinkable emulsions, suspensions or solutions for oral or injectable administration, sublingual tablets or suppositories. They may also be formulated into a sustained release form.
- excipients which may be used for these purposes include talc, magnesium phosphate, lactose or silica or the like.
- compositions of this invention may also be flavored, colored or coated with a wax or a plasticizer. It is to be understood that those skilled in the art of pharmaceutical formulation will be able to make a variety of formulations that would be within the scope of this disclosure and the appended claims, without departing from the spirit and teachings of the invention. It is intended that all such formulations be included in this invention.
- the invention may be practiced by administering serotonin-mediated neurotransmission stimulating compounds, for example, fenfluramines, to a subject as a single unit dose one or more times per day, or as a plurality of unit doses once or more times per day without deviating from the teachings of the invention.
- serotonin-mediated neurotransmission stimulating compounds for example, fenfluramines
- halogenated amphetamines may also be useful to treat stress in a subject who is suffering from the kind of stress alleviated by the fenfluramine treatments of the present invention.
- Such other useful drugs may include specific drugs that are not halogenated amphetamines including, but not limited to, effexor, nefazodone, bupropion, paroxetine, fluoxetine, and sertralin.
- Dexfenflurarnine and d,l-fenfluramine are known anorectic agents as disclosed in U.S. Patent No. 3,198,834.
- serotoninergic drugs in general nor dexfenflurarnine nor d,l-fenfluramine has been known to be effective as a treatment for stress in a patient.
- Fenfluramines are known to be effective drugs for treating obesity.
- the racemic mixture, d,l- fenflurarnine was disclosed in U.S. Patent 4,452,815, granted to Wurtman and Wurtman, as being effective for inhibiting the abnormal craving for carbohydrates which afflicts some people and which is associated with their obesity.
- Dexfenflurarnine is also indicated for use in treating patients who cannot control their eating habits or appetite.
- the use of dexfenflurarnine for this purpose was disclosed in U.S. Patent 4,309,445. In both of these patents the use proposed for fenfluramines was for treating a patient's appetite or craving for certain types of food.
- Fenfluramines are serotoninergic drugs that inhibit the abnormal craving for high carbohydrate foods, which leads to a positive caloric balance and subsequent obesity in certain people. Some, but not all, people benefit from the administration of dexfenfluramine by having their craving for certain foods inhibited.
- This above cited publication does not disclose or teach any use of dexfenfluramine or d,l-fenfluramines for treating stress itself in obese patients, or make any suggestion that these fenfluramines may be effective as a treatment for stress itself.
- the publication describes the serotoninergic fenfluramines as acting to facilitate weight loss in subjects in three ways: "They accelerate the onset of satiety and enhance basal metabolic rate by about 100 calories per day.
- dexfenflurarnine for treating animals inflicted with periodic pain is discussed in Dexfenfluramine: Effects on Food Intake in Various Animal Models, Neil E. Rowland and Janis
- This article discloses the administration of dexfenfluramine to rats exhibiting increased eating behavior in response to tail pinching.
- the tails of the rats were pinched as part of an experimental protocol, which was found to cause the rats to eat larger amounts of food than rats whose tails were not pinched.
- Dexfenfluramine (DF) was found to decrease the eating behavior of the tail pinched rats.
- Dexfenfluramine was known prior to the Rowland et al. article to depress eating activity, however, as shown in Wurtman et al., Science, vol. 198, pp. 1178-1180, December, 1977 incorporated by reference. The authors discussed the implications of their experiments with regard to stress-induced eating as follows on page S37 (DF indicating dexfenfluramine):
- DF Mild tail pressure induces eating and gnawing in rats, and this may be a model of stress- induced eating in humans.
- Garattini reported that DF potently inhibits tail pressure-induced eating, and that the DI 50 of 0.6 mg/kg is about one-half of the doses effective in the other paradigms reviewed so far. It was previously reported that racemic fenfluramine inhibits tail pressure-induced eating as well as concurrent behaviors such as gnawing, locomotion, and vocalization. In the study with DF, only the amount eaten was reported, rather than all oral behaviors. These data thus suggest that DF may be an especially potent inhibitor of stress- related eating. Further studies are needed to clarify the effect of DF on other oral behaviors, as well as whether it has 'antistress' effects along with its anorectic action.”
- dexfenfluramine inhibits eating in tail pinched rats. It was not previously known that serotoninergic drugs, for example dexfenfluramine or d,l-fenfluramine could be an effective treatment for stress.
- serotoninergic drugs for example dexfenfluramine or d,l-fenfluramine could be an effective treatment for stress.
- the authors of this article indicated only that fenfluramines inhibit tail pinching-induced eating and other behaviors stemming from the tail pinching protocol. They did not disclose that the fenfluramines could be used as treatments for reducing stress itself. Thus, Rowland et al. had no idea dexfenfluramine would exhibit any stress relieving activity per se. Indeed, it is doubtful that tail pinching and the consequent behavior from the rat induced by the tail pinching could serve as a meaningful, let alone reliable, model for the types of stress experienced by humans.
- the present invention is a novel treatment for stress and symptoms of stress in a subject.
- the applicants have discovered that administering Page 7, line 18.
- Administering serotoninergic drugs in general and fenfluramines in particular to a patient can bring about a reduction in the stress felt by patient and the symptoms of stress manifested by the patient.
- the treatment of stress and stress related symptoms of a patient with these compounds has not been reported previously.
- the present invention provides an appropriate treatment for stress in human patients, especially those suffering from stress-induced overeating.
- This invention is based on the discovery that the serotoninergic drugs, for example fenfluramines, such as d,l-fenfluramine, dexfenfluramine, or their salts can alleviate symptoms of stress in patients, when administered in effective amounts or at appropriate dosages.
- fenfluramines such as d,l-fenfluramine, dexfenfluramine, or their salts
- the present invention is directed to a method of treating a human subject exhibiting one or more symptoms of stress, which comprises administering to the subject an effective amount of a compound which enhances serotonin-mediated neurotransmission such as d,l- fenfluramine or dexfenfluramine, or a pharmaceutically acceptable salt thereof.
- a compound which enhances serotonin-mediated neurotransmission such as d,l- fenfluramine or dexfenfluramine, or a pharmaceutically acceptable salt thereof.
- an effective dose ranges from about 15 to about 150 mg/day, preferably from about 40 to about 80 mg/day.
- an effective dose ranges from about 5 to about 150 mg/day, preferably from about 15 to about 45 mg day.
- a treatment is provided which results in a reduction in the stress level of the patient experiencing emotional and other kinds of stress. Accordingly, it is an object of the invention to provide a treatment for stress perceived by a stress-induced overeating patient.
- the method comprises the administration of stimulators of serotonin-mediated neurotransmission such as fenfluramines to a patient with stress related symptoms.
- the method comprises the administration of effective amounts of either d,l-fenflurarnine, dexfenfluramine, or their salts.
- Other preferred embodiments provide detailed disclosure of the use of other compounds which enhance serotonin-mediated neurotransmission.
- a number of compounds are shown to enhance serotonin-mediated neurotransmission, and thus to be useful in treating humans with one or more symptoms of stress.
- These compounds include the following: d,l-fenfluramine, dexfenfluramine, tryptophan, lithium, chlorimipramine, cyanimipramine, fluoxetine, paroxetine, fluvoxamine, citalopram, femoxitine, cianopramine, sertraline, sibutramine, venlafaxine, ORG 6582, RU 25591, LM 5008, DU 24565, indalpine, CGP 6085/A, WY 25093, alaprociate, zimelidine, trazodone, amitriptyline, imipramine, trimipramine, doxepin, protriptyline, nortriptyline, dibenzoxazepine, deprenyl, isocarboxazide, phenelzine, tranylcypromine,
- 6-Chloro-2-(l-piperazinyl)pyrazine (MK-212), is obtained from Merck & Co., Inc. Whitehouse Station, N J.
- (S)-2-(4, 4, 7-trimethyl- 1 , 4-dihydro-indeno ( 1 , 2-B) pyrrol- 1 -yl- 1 - methylethylamine (Ro 60-175/ORG 35030) is obtained from F. Hoffmann-LaRoche Ltd., Basel, Switzerland.
- (S)-2-(Chloro-5-fluoro-indol-l-yl)-l -methylethylamine (Ro 60-0332/ORG 35035) is obtained from F.
- l-(2,5-dimethoxy-4-iodophenyl)-2- aminopropane DOI
- m-CPP l-(3- Chlorophenyl)piperazine
- the present invention as disclosed herein, also includes a method of making a medicament for treating stress, wherein the method comprises a step of mixing dexfenfluramine or d,l-fenfluramine with a pharmaceutically acceptable inert ingredient.
- a subgroup of obese individuals is identified, which individuals describe themselves as being unable to control their eating and who attempt to continue on a weight-reducing diet when experiencing emotional distress. These patients are treated for four months by enrolling them in a weight loss program that includes the administration of dexfenfluramine at 30 mg/day and which involves adherence to a reduced-calorie meal plan. The use of dexfenfluramine is found to enhance the ability of stressed overeaters to lose weight.
- Body Mass Index is defined as the weight in kilograms of a subject, divided by the subject's height in meters squared. Applicants conduct a survey of 189 female women of normal body weight (Body Mass Index
- CES-D Center for Environmental Studies Depression Form
- the obese, stressed patients receiving dexfenfluramine exhibit a weight loss of 12 ⁇ 1.8 pounds (5.45 ⁇ 0.82 kg) during the four month study period.
- the mean group score which at the beginning of the study is 9.4, fluctuates between 7 and 8 through the treatment period. Scores on the appetite and stress-induced overeating scales are also reduced compared with baseline levels. The initial score on the appetite and hunger scale is 10.5, which decreases to 5.0 during the treatment period.
- the summed Tension, Depression, Anger and Confusion scores on the POMS test at baseline is 24. This number drops to 16.8 during the study period. Moreover, the score on the emotional triggers to overeating report drops from 23.4 ⁇ 9.8 to 8.6 ⁇ 8.5 standard deviations by the end of the treatment period.
- treatment with a fenfluramine, dexfenfluramine specifically promotes the ability to control food intake and to lose weight among the stress-induced overeaters. More surprisingly, treatment reduces the indicators of stress in these patients.
- Example 1 involves treatment with d,l-fenfluramine at 30 mg/day.
- a preferred dosage is about 5 mg/day to about 150 mg/day.
- C.B. is a 48 year old white single female. She states in her screening forms that when she is upset or stressed she snacks on chocolate, popcorn, crackers, pretzels, and candy. She notes that she overeats when feeling frustrated, overwhelmed, and lonely and writes in answer to a question about whether she has difficulty in sticking to a diet when upset or stressed: "In the past when I am not in a formalized program, somehow my brain thinks I'm given a license to graze to placate my emotions when stressed. I tend to break all my own 'house' rules and eat anything I want.”
- Her starting weight is 216 pounds (98.2 kg) and after 4 months on dexfenfluramine, drops to 205.5 pounds (93.4 kg).
- Her baseline CES-D Mood Scores drop from 5 to 1 over the treatment period, and her emotional triggers decrease from a baseline of 23 to a value of 4 after four months. Hence, the treatment also greatly relieves her emotional distress.
- Example 2 involves treatment with dexfenfluramine hydrochloride at 30 mg/day.
- a preferred dosage range is from about 15 mg/day to about 45 mg/day.
- CM. is a 46 year old white married physician and mother of two. She reports in her initial screening report that when stressed, she snacks on chocolate, candy, chips, cookies, cake/pie, and popcorn. She writes: "I was on Weight Watchers, doing well even during vacation. But upon the start of the school year with all the schedules to handle, I was unable to keep with the program. Then the Christmas holidays were upon us and I was working really hard at the office. I started gaining weight and I could not stop eating. My appetite has tripled and it is hard for me to say no.”
- Example 3 involves the treatment of a 57 year old married female with lithium carbonate at 900 mg/day for four months.
- a preferred dose is about 600 mg/day to about 1500 mg/day.
- D.R. states in her screening forms that when she is upset or stressed she overeats on beer and crabs, as well as snack food such as potato chips and peanuts. This occurs when she feels stress or frustration from her employment as a government lawyer.
- Her starting weight is 246 pounds (111.8 kg) and after 4 months on lithium drops to 225 pounds (102.3 kg).
- Her baseline CES-D Mood Scores drop from 4 to 2 over the treatment period, and her emotional triggers decrease from a baseline of 15 to a value of 7 after four months. Hence, the treatment also greatly relieves her emotional distress and stress.
- Example 4 involves the treatment of a 35 year old single white female with fluoxetine hydrochloride at a dose from 20 mg/day for the first two weeks, 40 mg/day the second two weeks, 60 mg/day the third two weeks, and 80 mg/day through the end of the four month trial.
- the preferred dose is about 10 mg/day to about 160 mg/day.
- Example 5 involves the treatment of a 76 year old single white female with fluvoxamine maleate at a dose from 50 mg/day for the first week, 100 mg/day the second week, and 150 mg/day through the end of the four month trial.
- the preferred dose is about 25 mg/day to about 300 mg/day.
- J.B. complains of feelings of stress associated with social activities in the retirement community in which she lives. While clearly overweight, she does not complain about weight nor apparently recognizes her condition.
- Her starting weight is 302 pounds (137.3 kg) and after 4 months on dexfenfluramine, drops to 286 pounds (130 kg).
- Her baseline CES-D Mood Scores drop from 23 to 17 over the treatment period, and her emotional triggers decrease from a baseline of 34 to a value of 24 after four months. The treatment relieves her social stress and has the additional benefit of modest weight reduction.
- Example 6 involves the treatment of a 42 year old married white female with sertraline hydrochloride at a dose from 50 mg/day for the first week, 100 mg/day the second week, and 200 mg/day through the end of the four month trial.
- the preferred dose is about 25 mg/day to about 400 mg/day.
- P.Q. is employed as an accountant, has two small children, and experiences stress during the tax season. She eats between meals and reports wakening at night with anxiety which is relieved by consumption of ice cream.
- Example 7 involves the treatment of a 38 year old single white female with venlafaxine hydrochloride at a dose from 75 mg/day for the first week, 100 mg/day the second week, and 150 mg/day through the end of the four month trial.
- the preferred dose is about 50 mg/day to about 300 mg/day.
- Example 8 involves the treatment of a 44 year old single white female with amitriptyline hydrochloride at a dose from 75 mg/day for the first week, to 100 mg/day through the end of the four month trial.
- the preferred dose is about 50 mg/day to about 200 mg/day.
- E.E. reports stress from her employment as a dispatcher for a trucking company. Her discomfort is relieved by eating fried foods, especially fried potatoes.
- Her starting weight is pounds (90.0 kg) and at the end of 4 months on dexfenfluramine, her weight drops to pounds (82.6 kg).
- Her baseline CES-D Mood Scores drop from 29 to 18 over the treatment period, and her emotional triggers decrease from a baseline of 25 to a value of 3 after four months. Hence, the treatment also greatly relieves this patient's stress levels.
- Example 9 involves the treatment of a 30 year old married white female with trazodone hydrochloride at a dose of 100 mg/day in divided doses of 50 mg each through the end of the four month trial.
- the preferred dose is about 50 mg/day to about 200 mg/day.
- Her starting weight is 203 pounds (92.3 kg) and at the end of 4 months on sertraline, her weight drops to 160 pounds (72.7 kg).
- Her baseline CES-D Mood Scores drop from 9 to 1 over the treatment period, and her emotional triggers decrease from a baseline of 12 to a value of 3 after four months. Hence, the treatment relieves both the stress levels and the overweight.
- Example 10 involves the treatment of a 31 year old married white female with imipramine hydrochloride at an intramuscular dose of 75 mg/day through the end of the four month trial.
- the preferred dose is about 50 mg/day to about 150 mg/day.
- A.R. is employed at a consulting engineering firm and attends law school at night. Her regimented schedule and lack of exercise may contribute to her feelings of stress, which engenders over-eating.
- her emotional triggers decrease from a baseline of 22 to a value of 8 after four months.
- the treatment also greatly relieves her emotional distress.
- Example 11 involves the treatment of a married 42 year old white female with trimipramine maleate at a dose from 75 mg/day for the first week, to 100 mg/day through the end of the four month trial.
- the preferred dose is about 50 mg/day to about 200 mg/day.
- A.B. a teacher in a metropolitan school, reports stress which she attributes to her work and generally unhappy home life. She is unable to control episodic binge eating of ice cream and cake.
- Her starting weight is 180 pounds (81.8 kg) and at the end of 4 months on trimipramine, her weight drops to 158 pounds (71.8 kg).
- Her baseline CES-D Mood Scores drop from 25 to 13 over the treatment period, and her emotional triggers decrease from a baseline of 14 to a value of 3 after four months. Hence, the treatment also greatly relieves this patient's stress levels.
- Example 12 involves the treatment of a single 50 year old white female with phenelzine sulfate at a dose from 45 mg/day for the first week, to 60 mg/day through the end of the four month trial, each daily dose taken in three portions.
- the preferred dose is about 15 mg/day to about 120 mg/day.
- D.C. is a suburban bus driver and finds driving in traffic stressful. She constantly diets but is unable to successfully lose weight.
- Her starting weight is 184 pounds (83.6 kg) and at the end of 4 months on phenelzine, her weight drops to 174 pounds (79.1 kg).
- EXAMPLE 13 The effect of the hydrochloride salt of 6-Chloro-2-(l-piperazinyl)pyrazine (MK-212, which is obtained from Merck & Co., Inc. Whitehouse Station, NJ, on stress related eating in animals is determined through the observation of the effect of experimental compounds on stress-related eating in adult Sprague-Dawley rats. These rats are widely used as a recognized animal model useful in predicting the effect of serotoninergic drugs in humans.
- MK-212 6-Chloro-2-(l-piperazinyl)pyrazine
- the results are shown in Table 13.
- the average amount of food in mg which is consumed per rat 8 hours after initiation of the trials is shown in the following table.
- the relative amounts of stress eating with the amount at 0 mg/kg MK-212 as 100% is also shown in the Stress Eating row.
- the preferred daily dose of MK-212 is about 1 mg/kg body weight to about 10 mg/kg body weight.
- Table 13 shows MK-212 reduces stress-related eating which indicates MK-212 reduces stress.
- Example 14 shows the effect of (S)-2-(4, 4, 7-trimethyl-l, 4-dihydro-indol (1, 2-B) pyrrol- 1- yl-1 -methylethylamine (Ro 60-175/ORG 35030) which is obtained from F. Hoffmann-LaRoche Ltd., Basel, Switzerland, on stress-induced eating.
- the experiment is done as in Example 13 and Table 13 except that Ro 60-175/ORG 35030 is used instead of MK-212.
- the preferred daily dose of Ro 60- 175/ORG 35030 is about 1 mg/kg body weight to about 10 mg/kg body weight.
- Table 14 shows that Ro 60-175/ORG 35030 reduces stress related eating which indicates Ro 60-175/ORG 35030 reduces stress.
- Ro 60-0332/ORG 35035 The effect of (S)-2-(Chloro-5-fluoro-indol-l-yl)-l -methylethylamine (Ro 60-0332/ORG 35035) which is obtained from F. Hoffmann LaRoche Ltd., Basel, Switzerland, on eating in stressed rats is determined as in EXAMPLE 13 and Table 13, except Ro 60-0332/ORG 35035 is used rather than MK-212.
- the preferred daily dose of Ro 60-0332/ORG 35035 is about 1 mg/kg body weight to about 10 mg/kg body weight.
- Table 15 shows that Ro 60-0332/ORG 35035 reduces stress-related eating which indicates Ro 60-0332/ORG 35035 reduces stress.
Landscapes
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Cardiology (AREA)
- Emergency Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Inorganic Chemistry (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CA002337507A CA2337507A1 (en) | 1998-07-16 | 1999-07-16 | Composition for treatment of stress |
JP2000559836A JP2002520353A (en) | 1998-07-16 | 1999-07-16 | Compositions for the treatment of stress |
EP99934107A EP1096927A4 (en) | 1998-07-16 | 1999-07-16 | Composition for treatment of stress |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US9301398P | 1998-07-16 | 1998-07-16 | |
US60/093,013 | 1998-07-16 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2000003701A1 true WO2000003701A1 (en) | 2000-01-27 |
Family
ID=22236330
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1999/016153 WO2000003701A1 (en) | 1998-07-16 | 1999-07-16 | Composition for treatment of stress |
Country Status (4)
Country | Link |
---|---|
EP (1) | EP1096927A4 (en) |
JP (1) | JP2002520353A (en) |
CA (1) | CA2337507A1 (en) |
WO (1) | WO2000003701A1 (en) |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003082286A1 (en) * | 2002-04-03 | 2003-10-09 | Chemon Inc. | Quinoline derivatives, their preparation and pharmaceutical compositions comprising the same |
JP2005523334A (en) * | 2002-04-24 | 2005-08-04 | サイプレス バイオサイエンス, インコーポレイテッド | Prevention and treatment of functional disabilities, including stress related disorders |
US6960613B2 (en) | 1999-07-08 | 2005-11-01 | H. Lundbeck A/S | Treatment of neurotic disorders |
US10456373B2 (en) | 2015-10-23 | 2019-10-29 | Obshchestvo S Ogranichennoy Otvetstvennostyu “Normofarm” | Agent exhibiting anti-stress, anxiolytic and anti-depression activity, and composition based thereon |
US10519175B2 (en) | 2017-10-09 | 2019-12-31 | Compass Pathways Limited | Preparation of psilocybin, different polymorphic forms, intermediates, formulations and their use |
US11564935B2 (en) | 2019-04-17 | 2023-01-31 | Compass Pathfinder Limited | Method for treating anxiety disorders, headache disorders, and eating disorders with psilocybin |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5283263A (en) * | 1989-01-06 | 1994-02-01 | Norden Michael J | Method for treating certain psychiatric disorders and certain psychiatric symptoms |
US5561149A (en) * | 1986-07-30 | 1996-10-01 | Sandoz Ltd. | Use of certain imidazol carbazols in treating stress-related manic-depressive disorders |
US5597826A (en) * | 1994-09-14 | 1997-01-28 | Pfizer Inc. | Compositions containing sertraline and a 5-HT1D receptor agonist or antagonist |
US5852020A (en) * | 1996-11-22 | 1998-12-22 | Bristol-Myers Squibb Company | Nefazodone: use in treating post traumatic stress disorder |
US5916923A (en) * | 1993-06-28 | 1999-06-29 | American Home Products Corporation | Venlafaxine for the treatment of generalized anxiety disorder |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
SU1593659A1 (en) * | 1983-12-29 | 1990-09-23 | Московская ветеринарная академия им.К.И.Скрябина | Method of preventing stress of chickens |
JPH06699B2 (en) * | 1984-08-11 | 1994-01-05 | カネボウ食品株式会社 | Mental stability chewing gum |
KR950700063A (en) * | 1992-02-21 | 1995-01-16 | 베르너 발데크 | Brofaromine as an agent for treating post-traumatic stress |
FR2710916B1 (en) * | 1993-10-04 | 1995-12-22 | Pasteur Institut | Compounds of a peptide nature having a modulating activity of the serotonergic response; diagnostic and therapeutic applications. |
TW344661B (en) * | 1993-11-24 | 1998-11-11 | Lilly Co Eli | Pharmaceutical composition for treatment of incontinence |
US5502080A (en) * | 1994-11-01 | 1996-03-26 | Hitzig; Pietr | Combined use of dopamine and serotonin agonists in the treatment of allergic disorders |
JPH0940648A (en) * | 1995-08-02 | 1997-02-10 | Yamanouchi Pharmaceut Co Ltd | New 8-(2-aminoalkoxy)quinoline derivative |
-
1999
- 1999-07-16 EP EP99934107A patent/EP1096927A4/en not_active Withdrawn
- 1999-07-16 CA CA002337507A patent/CA2337507A1/en not_active Abandoned
- 1999-07-16 JP JP2000559836A patent/JP2002520353A/en active Pending
- 1999-07-16 WO PCT/US1999/016153 patent/WO2000003701A1/en not_active Application Discontinuation
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5561149A (en) * | 1986-07-30 | 1996-10-01 | Sandoz Ltd. | Use of certain imidazol carbazols in treating stress-related manic-depressive disorders |
US5283263A (en) * | 1989-01-06 | 1994-02-01 | Norden Michael J | Method for treating certain psychiatric disorders and certain psychiatric symptoms |
US5916923A (en) * | 1993-06-28 | 1999-06-29 | American Home Products Corporation | Venlafaxine for the treatment of generalized anxiety disorder |
US5597826A (en) * | 1994-09-14 | 1997-01-28 | Pfizer Inc. | Compositions containing sertraline and a 5-HT1D receptor agonist or antagonist |
US5852020A (en) * | 1996-11-22 | 1998-12-22 | Bristol-Myers Squibb Company | Nefazodone: use in treating post traumatic stress disorder |
Non-Patent Citations (1)
Title |
---|
See also references of EP1096927A4 * |
Cited By (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6960613B2 (en) | 1999-07-08 | 2005-11-01 | H. Lundbeck A/S | Treatment of neurotic disorders |
US7265151B2 (en) | 1999-07-08 | 2007-09-04 | H. Lundbeck A/S | Treatment of neurotic disorders |
US7271194B2 (en) | 1999-07-08 | 2007-09-18 | H. Lundbeck A/S | Treatment of neurotic disorders |
WO2003082286A1 (en) * | 2002-04-03 | 2003-10-09 | Chemon Inc. | Quinoline derivatives, their preparation and pharmaceutical compositions comprising the same |
JP2005523334A (en) * | 2002-04-24 | 2005-08-04 | サイプレス バイオサイエンス, インコーポレイテッド | Prevention and treatment of functional disabilities, including stress related disorders |
JP2010070573A (en) * | 2002-04-24 | 2010-04-02 | Cypress Bioscience Inc | Prevention and treatment of functional somatic disorder including stress-related disorder |
US10456373B2 (en) | 2015-10-23 | 2019-10-29 | Obshchestvo S Ogranichennoy Otvetstvennostyu “Normofarm” | Agent exhibiting anti-stress, anxiolytic and anti-depression activity, and composition based thereon |
US10947257B2 (en) | 2017-10-09 | 2021-03-16 | Compass Pathfinder Limited | Preparation of psilocybin, different polymorphic forms, intermediates, formulations and their use |
US10519175B2 (en) | 2017-10-09 | 2019-12-31 | Compass Pathways Limited | Preparation of psilocybin, different polymorphic forms, intermediates, formulations and their use |
US10954259B1 (en) | 2017-10-09 | 2021-03-23 | Compass Pathfinder Limited | Preparation of psilocybin, different polymorphic forms, intermediates, formulations and their use |
US11149044B2 (en) | 2017-10-09 | 2021-10-19 | Compass Pathfinder Limited | Preparation of psilocybin, different polymorphic forms, intermediates, formulations and their use |
US11180517B2 (en) | 2017-10-09 | 2021-11-23 | Compass Pathfinder Limited | Preparation of psilocybin, different polymorphic forms, intermediates, formulations and their use |
US11447510B2 (en) | 2017-10-09 | 2022-09-20 | Compass Pathfinder Limited | Preparation of psilocybin, different polymorphic forms, intermediates, formulations and their use |
US11505564B2 (en) | 2017-10-09 | 2022-11-22 | Compass Pathfinder Limited | Preparation of psilocybin, different polymorphic forms, intermediates, formulations and their use |
US11629159B2 (en) | 2017-10-09 | 2023-04-18 | Compass Pathfinder Limited | Preparation of psilocybin, different polymorphic forms, intermediates, formulations and their use |
US11851451B2 (en) | 2017-10-09 | 2023-12-26 | Compass Pathfinder Limited | Preparation of psilocybin, different polymorphic forms, intermediates, formulations and their use |
US11939346B2 (en) | 2017-10-09 | 2024-03-26 | Compass Pathfinder Limited | Preparation of psilocybin, different polymorphic forms, intermediates, formulations and their use |
US11564935B2 (en) | 2019-04-17 | 2023-01-31 | Compass Pathfinder Limited | Method for treating anxiety disorders, headache disorders, and eating disorders with psilocybin |
US11738035B2 (en) | 2019-04-17 | 2023-08-29 | Compass Pathfinder Limited | Method for treating anxiety disorders, headache disorders, and eating disorders with psilocybin |
Also Published As
Publication number | Publication date |
---|---|
CA2337507A1 (en) | 2000-01-27 |
EP1096927A4 (en) | 2002-09-04 |
JP2002520353A (en) | 2002-07-09 |
EP1096927A1 (en) | 2001-05-09 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US6579899B1 (en) | Composition for treatment of stress | |
Blackwell | Adverse effects of antidepressant drugs: part 1: monoamine oxidase inhibitors and tricyclics | |
Collins et al. | Clinical, biochemical, and neuropsychiatric evaluation of a patient with a contiguous gene syndrome due to a microdeletion Xp11. 3 including the Norrie disease locus and monoamine oxidase (MAOA and MAOB) genes | |
Silverstone et al. | Serotoninergic mechanisms in human feeding: the pharmacological evidence | |
Trenchard et al. | Naloxone reduces the food intake of normal human volunteers | |
Goodwin et al. | A psychobiological approach to affective illness | |
AU2006235257B2 (en) | Methods for treating anxiety related disorders | |
US20020040054A1 (en) | Comprehensive pharmacologic therapy for treatment of obesity | |
CN113939298A (en) | Methods for treating depression | |
US7268161B2 (en) | Comprehensive pharmacologic therapy for treatment of obesity including cysteine | |
US4452815A (en) | Method of utilizing d,l-fenfluramine for modifying feeding behavior | |
EP0053175B1 (en) | Use of d-fenfluramine for the manufacture of a medicament for modifying feeding behavior | |
Finer | Present and future pharmacological approaches | |
US20090012177A1 (en) | Treatment of psychiatric disorders using entacapone, tolcapone and other COMT inhibitor or MB-COMT inhibitor drugs | |
WO2000003701A1 (en) | Composition for treatment of stress | |
Burd et al. | Anticonvulsant medications: an latrogenic cause of tic disorders | |
US20090281112A1 (en) | Adatanserin and metabolites thereof for treatment of attention deficit disorder, anxiety, depression, sexual dysfunction, and other disorders | |
Vivero et al. | A close look at fenfluramine and dexfenfluramine | |
Billiard et al. | Narcolepsy | |
Rubino et al. | A review of topiramate and phentermine: a combined therapeutic approach for obesity | |
Moorhouse et al. | Carbohydrate Craving by Alcohol‐Dependent Men During Sobriety: Relationship to Nutrition and Serotonergic Function | |
Trygstad | Drugs in the treatment of bulimia nervosa | |
AU743788B2 (en) | Method of improving disturbed behavior and elevating mood in humans | |
WO2020158415A1 (en) | Composition for competitive inhibition of orexin receptors | |
JPS6245523A (en) | Anorectic |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): CA JP |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
ENP | Entry into the national phase |
Ref country code: JP Ref document number: 2000 559836 Kind code of ref document: A Format of ref document f/p: F |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1999934107 Country of ref document: EP |
|
WWP | Wipo information: published in national office |
Ref document number: 1999934107 Country of ref document: EP |
|
ENP | Entry into the national phase |
Ref document number: 2337507 Country of ref document: CA |
|
WWW | Wipo information: withdrawn in national office |
Ref document number: 1999934107 Country of ref document: EP |