US2902404A - New sedatives and anticonvulsants - Google Patents
New sedatives and anticonvulsants Download PDFInfo
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- US2902404A US2902404A US698369A US69836957A US2902404A US 2902404 A US2902404 A US 2902404A US 698369 A US698369 A US 698369A US 69836957 A US69836957 A US 69836957A US 2902404 A US2902404 A US 2902404A
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- new
- anticonvulsants
- sedatives
- nitro
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- 239000001961 anticonvulsive agent Substances 0.000 title description 6
- 239000000932 sedative agent Substances 0.000 title description 4
- 229940125681 anticonvulsant agent Drugs 0.000 title description 3
- 229940125723 sedative agent Drugs 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims description 17
- 239000002552 dosage form Substances 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 3
- 230000036524 ataraxia Effects 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 3
- 241000699670 Mus sp. Species 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- 239000002249 anxiolytic agent Substances 0.000 description 7
- CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical compound C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 description 6
- 206010010904 Convulsion Diseases 0.000 description 5
- NPPQSCRMBWNHMW-UHFFFAOYSA-N Meprobamate Chemical compound NC(=O)OCC(C)(CCC)COC(N)=O NPPQSCRMBWNHMW-UHFFFAOYSA-N 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 4
- 229960004815 meprobamate Drugs 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 101100205030 Caenorhabditis elegans hars-1 gene Proteins 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 230000001773 anti-convulsant effect Effects 0.000 description 3
- 230000036461 convulsion Effects 0.000 description 3
- 150000002009 diols Chemical class 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 229960003965 antiepileptics Drugs 0.000 description 2
- 239000003874 central nervous system depressant Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 230000000147 hypnotic effect Effects 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- JWDYCNIAQWPBHD-UHFFFAOYSA-N 1-(2-methylphenyl)glycerol Chemical compound CC1=CC=CC=C1OCC(O)CO JWDYCNIAQWPBHD-UHFFFAOYSA-N 0.000 description 1
- OMILNLGCVJMNIV-UHFFFAOYSA-N 2-nitro-2-propylpropane-1,3-diol Chemical compound CCCC(CO)(CO)[N+]([O-])=O OMILNLGCVJMNIV-UHFFFAOYSA-N 0.000 description 1
- 241000220479 Acacia Species 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 208000009132 Catalepsy Diseases 0.000 description 1
- 206010009346 Clonus Diseases 0.000 description 1
- RRHGJUQNOFWUDK-UHFFFAOYSA-N Isoprene Chemical compound CC(=C)C=C RRHGJUQNOFWUDK-UHFFFAOYSA-N 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- 206010047853 Waxy flexibility Diseases 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000037424 autonomic function Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 239000003179 convulsant agent Substances 0.000 description 1
- 230000002920 convulsive effect Effects 0.000 description 1
- 230000001815 facial effect Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 230000003387 muscular Effects 0.000 description 1
- 230000000803 paradoxical effect Effects 0.000 description 1
- 210000001152 parietal lobe Anatomy 0.000 description 1
- 239000002510 pyrogen Substances 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
- 230000002936 tranquilizing effect Effects 0.000 description 1
- 229940105642 tridione Drugs 0.000 description 1
- IRYJRGCIQBGHIV-UHFFFAOYSA-N trimethadione Chemical compound CN1C(=O)OC(C)(C)C1=O IRYJRGCIQBGHIV-UHFFFAOYSA-N 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/13—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by hydroxy groups
- C07C205/14—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by hydroxy groups having nitro groups and hydroxy groups bound to acyclic carbon atoms
- C07C205/15—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by hydroxy groups having nitro groups and hydroxy groups bound to acyclic carbon atoms of a saturated carbon skeleton
Definitions
- ACD Anticonvulsant dose.
- ALD Anti1ethal dose.
- AODso relaxant ataraxic or antiphobic drugs depending upon the particular form of mental ailment for which they have been found to be most suitable.
- the relaxant drugs ordinarily produce reversible paralysis of the voluntary muscles without significantly affecting autonomic functions.
- One of the most widely used drugs of this type at the present time is Z-methyl-Z-npropyl-1,3-propanediol dicarbamate, generally known as meprobamate.
- meprobamate is not equally effective with all patients and it produces undesirable side etfects in many cases including such unfavorable efiects as cutaneous, muscular, gastrointestinal, and paradoxical cerebral efiects.
- the desirability of having available drugs not subject to all or even a portion of these undesirable effects and in general are even more effective as relaxants appears obvious.
- propanediol 2-nitro-2-isopropyl-1,3-propanediol, 2-nitro- Z-methyl-l-propanol, Z-nitro-Z-methyl-l-butanol, B-nitro- 2-butanol, and 4-nitro-3-hexanol.
- mice were tested by the method of E. A. Swinyard (J. Am. Pharm. Ass0c., scientific ed., 38, 201, (1949)), to determine the electroshock convulsive threshold of mice determined by using a stimulus delivered from an electroshock apparatus.
- the mice were stimulated with a small rat electrode placed on the parietal lobes just behind the eyes. They were restrained only by the hand and released immediately after a stimulation lasting 0.2 second.
- the compound tested was dissolved in water and 300 rug/kg. administered intraperitoneally to the test animal. Twenty minutes after administration of the compound maximal electroshock seizure (MES) and normal electroshock threshold (NET) tests were made.
- MES maximal electroshock seizure
- NET normal electroshock threshold
- the end point for MES tests was abolition of the extension of the hind legs during the tonic phase of the seizure when a stimulus five times the threshold was employed. Absence of facial clonus for a period of 10 seconds following stimulation with a shock 20% greater thanthreshold was taken as the end point for the NET tests.
- Table IV shows a comparison of certain of my compounds with the relaxant meprobamate. In each case the 'compoundwas administered orally 'to the test animals (mice) and the time of reaction determined. The values are in minutes except where otherwise indicated.
- composition in unit dosage form for use in producing ataraxia containing as the essential active ingredient 0.25-0.5 g. of a compound having the structural formula:
- R is hydrogen, methyl, ethyl, n-propyl, and isopropyl
- R is hydroxymethyl, l-hydroxyethyl, and l-hydroxypropyl
- R is methyl, ethyl and hydroxymethyl
- composition in unit dosage form for use in producing ataraxia containing as the essential active ingredient 0.25-0.5 g. of 2-nitro-2-propyl-1,3-propanediol. 3.
- the process of effecting ataraxic efiects in the living human body which comprises administering a compound having the structural formula:
- R OR l where R is hydrogen, methyl, ethyl, n-propyl, and isopropyl, R is 'hydroxymethyl, l-hydroxyethyl, and l-hydroxyp'ropyl, and R is methyl, ethyl and hydroxymethyl.
- Time of hypnosis 12 20 none 7 15 none... none.
- Time of catalepsy none none 30 none. none.. none.
- Time of onset of recovery 4 hrs 2 hrs 1% hrs 4% hrs- 1% hrs-- 1 hr 30.
- Time of complete recovery 8 hrs 5% hrs" 2 hrs 8 hrs-. 5 hrs 2 hrs 2 hrs.
- My new sedatives and anticonvulsants are preferably administered orally in the form of tablets, capsules or other suitable forms.
- Preferred doses range from 0.25 to 0.50 gm., two to four times daily, or single doses of 0.5 to 1.0 gm. daily.
- a process of effecting ataraxic effects in the living human body which comprises administering in oral unit dosage form 2-nitro 2-propyl-l,3-propanediol in amounts ranging from 1.0 g. to 2.0 g; per day.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
United States Patent NEW SEDATIVES AND ANTICONVULSANTS Joseph N. Spencer, Media, Pa., assignor to Commercial Solvents Corporation, Terre Haute, Ind., a corpora tion of Maryland No Drawing. Application November 25, 1957 Serial No. 698,369
4 Claims. (Cl. 167-65) 2,902,404 Patented Sept. 1, 1959 ated by comparing the anticonvulsant action of the drugs in male, white mice, weighing 18 to 22 g. The compounds being evaluated were dissolved in pyrogen free water or suspended in 10% acacia and the desired dose administered either orally or intraperitoneally. When the compounds were administered intraperitoneally, 100 rags/kg. of Metrazol were given intraperitoneally simultaneously with the test compound. In the oral studies, 100 mgs./ kg. of Metrazol were given intraperitoneally minutes after the compound. All mice were observed one hour for convulsions and 18-24 hours for death. Five mice were employed at each level and a maximum dose of 500 mgs/kg. was used. Compounds incapable of preventing Metrazol convulsions at this level were considered too inactive to warrant additional studies. Table I below gives the results of convulsant studies on my new relaxants and compares them with the previously known relaxant Tridione and myanesin. The upper row of figures following each compound represents results from oral administration, and the lower row intraperitoneal administration.
Table I LDso, ACDso, ALDso, LDWI LDM mg./kg. mg./kg mg./kg .AODw ALDm -w pr -p p 3;; 1 py fi-P p ij 2 &2 p 1, 020:1:112 325:l;63 US$28 2.8 5.7 2 f 2 methyl 1 Pmpanol 800=b121 175fl=33 ss22 4. e 9. 3 2-n 1tro-Zmethyl-l-butanol 8205578 205510 142530 4. 0 5.8 Trldm e I 1, 3603:96 380:1:48 122:1:31 3. 6 11. 1 Myanesm-B-(o-t0loxy)-1,2-propaned1o1 6105:10 7. 6
ACD =Anticonvulsant dose.
ALD =Anti1ethal dose.
AODso relaxant, ataraxic or antiphobic drugs depending upon the particular form of mental ailment for which they have been found to be most suitable.
The relaxant drugs ordinarily produce reversible paralysis of the voluntary muscles without significantly affecting autonomic functions. One of the most widely used drugs of this type at the present time is Z-methyl-Z-npropyl-1,3-propanediol dicarbamate, generally known as meprobamate. Like most drugs, however, meprobamate is not equally effective with all patients and it produces undesirable side etfects in many cases including such unfavorable efiects as cutaneous, muscular, gastrointestinal, and paradoxical cerebral efiects. The desirability of having available drugs not subject to all or even a portion of these undesirable effects and in general are even more effective as relaxants appears obvious.
I have discovered that the compounds designated by the structural formula amples of such compounds include 2-nitro-2-n-propyl-l,3-
propanediol, 2-nitro-2-isopropyl-1,3-propanediol, 2-nitro- Z-methyl-l-propanol, Z-nitro-Z-methyl-l-butanol, B-nitro- 2-butanol, and 4-nitro-3-hexanol.
My new sedative and anticonvulsant drugs were evalu- Table II shows the duration of anticonvulsant activity of my new relaxants in mice.
1 Control mice given Metrazol simultaneously with 300 rug/kg. of this compound had typical Metrazol convulsions 821- minutes after Metrazol was administered.
Certain of my compounds were tested by the method of E. A. Swinyard (J. Am. Pharm. Ass0c., scientific ed., 38, 201, (1949)), to determine the electroshock convulsive threshold of mice determined by using a stimulus delivered from an electroshock apparatus. The mice were stimulated with a small rat electrode placed on the parietal lobes just behind the eyes. They were restrained only by the hand and released immediately after a stimulation lasting 0.2 second. The compound tested was dissolved in water and 300 rug/kg. administered intraperitoneally to the test animal. Twenty minutes after administration of the compound maximal electroshock seizure (MES) and normal electroshock threshold (NET) tests were made. The end point for MES tests was abolition of the extension of the hind legs during the tonic phase of the seizure when a stimulus five times the threshold was employed. Absence of facial clonus for a period of 10 seconds following stimulation with a shock 20% greater thanthreshold was taken as the end point for the NET tests.
' 'Table III below gives results for certain of my compounds tested in this manner.
Toxie doses. 1 2 At 200 mg.lkg.
Table IV below shows a comparison of certain of my compounds with the relaxant meprobamate. In each case the 'compoundwas administered orally 'to the test animals (mice) and the time of reaction determined. The values are in minutes except where otherwise indicated.
Now having described my invention what I claim is: 1'. A composition in unit dosage form for use in producing ataraxia containing as the essential active ingredient 0.25-0.5 g. of a compound having the structural formula:
N R J-R 1% Where R is hydrogen, methyl, ethyl, n-propyl, and isopropyl, R is hydroxymethyl, l-hydroxyethyl, and l-hydroxypropyl, and R is methyl, ethyl and hydroxymethyl.
2. A composition in unit dosage form for use in producing ataraxia containing as the essential active ingredient 0.25-0.5 g. of 2-nitro-2-propyl-1,3-propanediol. 3. The process of effecting ataraxic efiects in the living human body which comprises administering a compound having the structural formula:
R OR l where R is hydrogen, methyl, ethyl, n-propyl, and isopropyl, R is 'hydroxymethyl, l-hydroxyethyl, and l-hydroxyp'ropyl, and R is methyl, ethyl and hydroxymethyl.
Table IV 2-methy1-2-n-propy1-1,3- 2-nitro-2-n-propyl-1,3- 4-n1tro-3- propanediol (meprobamate) propanediol dicarbamate hexanol 1,600 800 400 1,600 800 V 400 400 nag/kg mg./kg. mgJkg. mg./kg. rug/kg. mg./kg. rug/kg.
Time of first evidence of disturb- 2- 2- 3- 1 2 2.
ance. Time of greatest depression 7 10 3.; 6 18 2. Time of hypnosis 12 20 none 7 15 none... none. Time of catalepsy none none 30 none. none.. none. Time of onset of recovery 4 hrs 2 hrs 1% hrs 4% hrs- 1% hrs-- 1 hr 30. Time of complete recovery 8 hrs 5% hrs" 2 hrs 8 hrs-. 5 hrs 2 hrs 2 hrs.
I am aware of the fact that certain substituted diols and dicarbamates of substituted diols possess central depressant properties. I have now discovered, however, that the introduction of the N0 group into substituted diols gives central nervous system depressants of equal and in some cases decidedly higher eiiectiveness than previously known drugs of this type and which possess the additional advantage of being relatively free from the concomitant depression or anesthesia generally induced by previously available drugs of this class.
The results with animals shown in the tables above have been confirmed by clinical use in man. One to two 0.25 g. doses administered four times daily produced a generally tranquilizing effect and in some patients an hypnotic effect as well.
My new sedatives and anticonvulsants are preferably administered orally in the form of tablets, capsules or other suitable forms. Preferred doses range from 0.25 to 0.50 gm., two to four times daily, or single doses of 0.5 to 1.0 gm. daily.
4. A process of effecting ataraxic effects in the living human body which comprises administering in oral unit dosage form 2-nitro 2-propyl-l,3-propanediol in amounts ranging from 1.0 g. to 2.0 g; per day.
:References Cited in the file of'this patent UNITED STATES PATENTS Vanderbilt Oct. 4, 1938 Bass et al. Dec. 6, 1938 OTHER REFERENCES Brit. Med. 1., Mar. 22, 1958, pp.
UNITED STATES PATENT; OFFICE CERTIFICATE OF CORRECTION Patent No. 2,902,404 September 1 1959 Joseph N, Spencer It is hereby certified that error appears in the printed specification of the above numbered patent requiring correction and that the said Letters Patent should read as corrected below.
Columns 3. and 4, Table IV, the heading over columns 2, 1, and 4 thereof, for 2methyl2-n-propyll 3&propanedi0l (mepr0bamate)" read 2-methyl-2n- -propyl-l, 3-propanediol dicarbamate (meprobamate) same columns 3 and 4 Table IV the heading over columns 5, 6 and 7 thereof for "'.2nitro2 n-pr0pyll,;3propanediol dicarbamate'? read 2-nitro2-n-- propyll,3propanediol Signed and sealed this 9th day of August 1960.,
(SEAL) Attest:
KARL H AXLINE ROBERT C. WATSON Attesting Officer Commissioner of Patents
Claims (1)
1. A COMPOSITION IN UNIT DOSAGE FORM FOR USE IN PRODUCING ATARAXIA CONTAINING AS THE ESSENTIAL ACTIVE INGREDIENT 0.25-0.5 G. OF A COMPOUND HAVING THE STRUCTURAL FORMULA:
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US698369A US2902404A (en) | 1957-11-25 | 1957-11-25 | New sedatives and anticonvulsants |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US698369A US2902404A (en) | 1957-11-25 | 1957-11-25 | New sedatives and anticonvulsants |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US2902404A true US2902404A (en) | 1959-09-01 |
Family
ID=24804951
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US698369A Expired - Lifetime US2902404A (en) | 1957-11-25 | 1957-11-25 | New sedatives and anticonvulsants |
Country Status (1)
| Country | Link |
|---|---|
| US (1) | US2902404A (en) |
Cited By (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3037984A (en) * | 1960-01-27 | 1962-06-05 | Lakeside Lab Inc | Derivatives of n-amino-1, 2, 3, 4-tetrahydroisoquinoline |
| US3072720A (en) * | 1960-04-07 | 1963-01-08 | Upjohn Co | Novel n-arylsulfonyl-n'-(2, 5-endomethylene-1, 2, 5, 6-tetrahydrobenzyl) ureas |
| US3072530A (en) * | 1958-09-12 | 1963-01-08 | Sandoz Ag | Therapeutic indoles for psychic stimulation and relief of mental depression |
| US3078214A (en) * | 1958-09-12 | 1963-02-19 | Sandoz Ag | Treatment of mental disturbances with esters of indoles |
| US3095424A (en) * | 1961-08-14 | 1963-06-25 | Mead Johnson & Co | 3, 5-diaryl-3-pyrrolidinols |
| US3118907A (en) * | 1961-08-14 | 1964-01-21 | Mead Johnson & Co | 3-substituted-3-pyrrolidinols |
| US3118906A (en) * | 1959-02-12 | 1964-01-21 | Mead Johnson & Co | 3-substituted-3-pyrrolidinols |
| US3124593A (en) * | 1964-03-10 | Pharmacologically active z | ||
| US3125583A (en) * | 1964-03-17 | Hjnc oxchaxohxchc o oh | ||
| US3135766A (en) * | 1961-10-03 | 1964-06-02 | Mead Johnson & Co | 3-substituted-3-pyrrolidinols |
| US3157671A (en) * | 1964-11-17 | Ljl-diethyl-a-hydroxypyrrolidimum | ||
| US3168526A (en) * | 1960-04-20 | 1965-02-02 | Upjohn Co | Derivatives of 3-(2-nitroethyl)-indole |
| US3188329A (en) * | 1962-04-10 | 1965-06-08 | Colgate Palmolive Co | Diuretic anils |
| US3232950A (en) * | 1962-01-31 | 1966-02-01 | Schering Corp | 5-(2'-picolyl)5-hydroxy-dibenzo[a,d]cyclohepta[1,4]diene and acid addition salts thereof |
| US3312694A (en) * | 1962-07-13 | 1967-04-04 | Chinoin Gyogyszer Es Vegyeszet | N-tertiary aminomethyl-succinimides |
| US3349124A (en) * | 1957-05-20 | 1967-10-24 | Pfizer & Co C | Oral antidiabetic agent |
| US3384757A (en) * | 1955-10-15 | 1968-05-21 | Hoechst Ag | Benzene sulfonyl ureas and process for their preparation |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2132330A (en) * | 1937-06-30 | 1938-10-04 | Purdue Research Foundation | Preparation of nitrohydroxy compounds |
| US2139120A (en) * | 1937-06-07 | 1938-12-06 | Purdue Research Foundation | Process for the production of nitrohydroxy compounds |
-
1957
- 1957-11-25 US US698369A patent/US2902404A/en not_active Expired - Lifetime
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2139120A (en) * | 1937-06-07 | 1938-12-06 | Purdue Research Foundation | Process for the production of nitrohydroxy compounds |
| US2132330A (en) * | 1937-06-30 | 1938-10-04 | Purdue Research Foundation | Preparation of nitrohydroxy compounds |
Cited By (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3124593A (en) * | 1964-03-10 | Pharmacologically active z | ||
| US3125583A (en) * | 1964-03-17 | Hjnc oxchaxohxchc o oh | ||
| US3157671A (en) * | 1964-11-17 | Ljl-diethyl-a-hydroxypyrrolidimum | ||
| US3384757A (en) * | 1955-10-15 | 1968-05-21 | Hoechst Ag | Benzene sulfonyl ureas and process for their preparation |
| US3349124A (en) * | 1957-05-20 | 1967-10-24 | Pfizer & Co C | Oral antidiabetic agent |
| US3072530A (en) * | 1958-09-12 | 1963-01-08 | Sandoz Ag | Therapeutic indoles for psychic stimulation and relief of mental depression |
| US3078214A (en) * | 1958-09-12 | 1963-02-19 | Sandoz Ag | Treatment of mental disturbances with esters of indoles |
| US3118906A (en) * | 1959-02-12 | 1964-01-21 | Mead Johnson & Co | 3-substituted-3-pyrrolidinols |
| US3037984A (en) * | 1960-01-27 | 1962-06-05 | Lakeside Lab Inc | Derivatives of n-amino-1, 2, 3, 4-tetrahydroisoquinoline |
| US3072720A (en) * | 1960-04-07 | 1963-01-08 | Upjohn Co | Novel n-arylsulfonyl-n'-(2, 5-endomethylene-1, 2, 5, 6-tetrahydrobenzyl) ureas |
| US3168526A (en) * | 1960-04-20 | 1965-02-02 | Upjohn Co | Derivatives of 3-(2-nitroethyl)-indole |
| US3095424A (en) * | 1961-08-14 | 1963-06-25 | Mead Johnson & Co | 3, 5-diaryl-3-pyrrolidinols |
| US3118907A (en) * | 1961-08-14 | 1964-01-21 | Mead Johnson & Co | 3-substituted-3-pyrrolidinols |
| US3135766A (en) * | 1961-10-03 | 1964-06-02 | Mead Johnson & Co | 3-substituted-3-pyrrolidinols |
| US3232950A (en) * | 1962-01-31 | 1966-02-01 | Schering Corp | 5-(2'-picolyl)5-hydroxy-dibenzo[a,d]cyclohepta[1,4]diene and acid addition salts thereof |
| US3188329A (en) * | 1962-04-10 | 1965-06-08 | Colgate Palmolive Co | Diuretic anils |
| US3312694A (en) * | 1962-07-13 | 1967-04-04 | Chinoin Gyogyszer Es Vegyeszet | N-tertiary aminomethyl-succinimides |
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