US2955073A - Method of treating febrile convulsions - Google Patents
Method of treating febrile convulsions Download PDFInfo
- Publication number
- US2955073A US2955073A US738982A US73898258A US2955073A US 2955073 A US2955073 A US 2955073A US 738982 A US738982 A US 738982A US 73898258 A US73898258 A US 73898258A US 2955073 A US2955073 A US 2955073A
- Authority
- US
- United States
- Prior art keywords
- seizures
- metrazol
- febrile convulsions
- phenylbarbital
- convulsions
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 208000002091 Febrile Seizures Diseases 0.000 title claims description 13
- 238000000034 method Methods 0.000 title claims description 8
- ILORKHQGIMGDFN-UHFFFAOYSA-N phetharbital Chemical compound O=C1C(CC)(CC)C(=O)NC(=O)N1C1=CC=CC=C1 ILORKHQGIMGDFN-UHFFFAOYSA-N 0.000 claims description 10
- 238000011282 treatment Methods 0.000 claims description 7
- 206010010904 Convulsion Diseases 0.000 description 24
- CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical compound C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 description 10
- 229940079593 drug Drugs 0.000 description 10
- 239000003814 drug Substances 0.000 description 10
- 238000012360 testing method Methods 0.000 description 8
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 239000001961 anticonvulsive agent Substances 0.000 description 4
- 230000002566 clonic effect Effects 0.000 description 4
- 231100000419 toxicity Toxicity 0.000 description 4
- 230000001988 toxicity Effects 0.000 description 4
- 208000007101 Muscle Cramp Diseases 0.000 description 3
- 208000005392 Spasm Diseases 0.000 description 3
- 230000001754 anti-pyretic effect Effects 0.000 description 3
- 230000036760 body temperature Effects 0.000 description 3
- 230000002920 convulsive effect Effects 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 230000001256 tonic effect Effects 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- 235000005979 Citrus limon Nutrition 0.000 description 2
- 244000131522 Citrus pyriformis Species 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 235000001188 Peltandra virginica Nutrition 0.000 description 2
- 206010034759 Petit mal epilepsy Diseases 0.000 description 2
- CXOFVDLJLONNDW-UHFFFAOYSA-N Phenytoin Chemical compound N1C(=O)NC(=O)C1(C=1C=CC=CC=1)C1=CC=CC=C1 CXOFVDLJLONNDW-UHFFFAOYSA-N 0.000 description 2
- 244000197580 Poria cocos Species 0.000 description 2
- 235000008599 Poria cocos Nutrition 0.000 description 2
- 206010037660 Pyrexia Diseases 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 230000001773 anti-convulsant effect Effects 0.000 description 2
- 229940125681 anticonvulsant agent Drugs 0.000 description 2
- 229960003965 antiepileptics Drugs 0.000 description 2
- 239000002221 antipyretic Substances 0.000 description 2
- 150000007656 barbituric acids Chemical class 0.000 description 2
- 230000036461 convulsion Effects 0.000 description 2
- 206010015037 epilepsy Diseases 0.000 description 2
- 206010016284 febrile convulsion Diseases 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 2
- 229960002695 phenobarbital Drugs 0.000 description 2
- 229960002036 phenytoin Drugs 0.000 description 2
- 229920001592 potato starch Polymers 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 206010001497 Agitation Diseases 0.000 description 1
- 206010003591 Ataxia Diseases 0.000 description 1
- 206010009346 Clonus Diseases 0.000 description 1
- 206010010947 Coordination abnormal Diseases 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- NPPQSCRMBWNHMW-UHFFFAOYSA-N Meprobamate Chemical compound NC(=O)OCC(C)(CCC)COC(N)=O NPPQSCRMBWNHMW-UHFFFAOYSA-N 0.000 description 1
- FWJKNZONDWOGMI-UHFFFAOYSA-N Metharbital Chemical compound CCC1(CC)C(=O)NC(=O)N(C)C1=O FWJKNZONDWOGMI-UHFFFAOYSA-N 0.000 description 1
- 208000036572 Myoclonic epilepsy Diseases 0.000 description 1
- 206010039897 Sedation Diseases 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- BZKPWHYZMXOIDC-UHFFFAOYSA-N acetazolamide Chemical compound CC(=O)NC1=NN=C(S(N)(=O)=O)S1 BZKPWHYZMXOIDC-UHFFFAOYSA-N 0.000 description 1
- 229960000571 acetazolamide Drugs 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 229940125716 antipyretic agent Drugs 0.000 description 1
- 229940125717 barbiturate Drugs 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000005021 gait Effects 0.000 description 1
- 208000028326 generalized seizure Diseases 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000002977 hyperthermial effect Effects 0.000 description 1
- 208000016290 incoordination Diseases 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229960004815 meprobamate Drugs 0.000 description 1
- 229960002057 metharbital Drugs 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000028527 righting reflex Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 231100000161 signs of toxicity Toxicity 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 231100000816 toxic dose Toxicity 0.000 description 1
- 231100000820 toxicity test Toxicity 0.000 description 1
- 229960004453 trimethadione 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
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—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
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
- A61K31/515—Barbituric acids; Derivatives thereof, e.g. sodium pentobarbital
Definitions
- Treatments available at the present time are unsatisfac tory, often being inadequate to control the convulsions and difiicult to apply.
- One method frequently'used is to cool the patientby means of ice packs.
- Another method is to place the patient under heavy-sedation'by meansof anesthetic barbiturates until lossof consciousness is'appreparation for the alleviaproached. Hospitalization is frequently required.
- C'ertain anticonvulsants, such as diphenylhydantoin may actually exacerbate the seizures.
- N-phenylbarbital protected 50 percent of mice from metrazol seizures; 2 U 5 mg./kg. protected 50 percent of mice from tonic component of the maximal electroshock seizure.
- N-phenylbarbital had a unique action different from that of even very close relatives (note Nos. 402-4). Accordingly the more fundamental test procedure was applied to this compound in comparison with drugs of known properties.
- trimethadione, meprobamate and phenobarbital of value in the treatment of petit mal and myoclonic epilepsies, were eltective in the control of febrile seizures, but large and toxic doses were required to abolish the clonns completely.
- Such drugs are also effective against the clonic metrazol-induced seizure.
- Diphenylhydantoin which is ineffective against experimen- 3 tal metrazol seizures, and in petit mal and is used primarily for treatment of tonic major seizures, failed to control the febrile convulsion and indeed, exacerbated the clonic pattern.
- Acetazolamide raised the threshold convulsive temperature but did not abolish clonus completely; it was also inactive against metrazol-induced seizures.
- N-phenylbarbital proved remarkably efiective against both metrazol and fever-induced seizures.
- it was strongly antipyretic and its action was relatively rapid on oral administration.
- phenobarbital and ,metharbital Compared with phenobarbital and ,metharbital, its toxicity was low and its protective therapeutic index (ratio of toxic to efiective dose) was high.
- the compound has the additional advantage of being free from toxic side-effects at doses which eifeotively protect against febrile convulsions.
- the side-effects which often may be observed with other compounds may be detected by the following tests: (1) the righting reflex test, (2) the positional sense test, (3) the gait stance test, (4) the muscle tone test, and (5) the equilibrium test.
- Graded oral doses gave a TD of 190 mg./kg. for these neural toxicity tests.
- the lethal action of B.W. 401 required much higher doses.
- the LD was found to be 900 mg./ kg.
- drug may be presented in capsules, tablets or in the form of an elixir or syrup.
- the latter is of particular convenience in treating young children.
- Example Five hundred and thirty g. of N-phenylbarbital is ground thoroughly and sifted through a mesh sieve. It is then mixed with 116.6 g. of dried potato starch and again passed through a 60 mesh sieve. The powder is then granulated twice each time with cc. of 20 percent Feculose solution.
- Feculose is the tradename of a partially degraded starch preparation consisting largely of starch and high-molecular dextrins. The granules are dried over-night at F. and broken up so as to pass through a 24 mesh sieve. To this was added a mixture passed through a 60 mesh sieve of 13.25 g. of dried potato starch and 7.95 g. of stearic acid. The whole was mixed thoroughly and fed into a tabletting machine using #74 scored punches. The tablets so prepared weigh 139.5 mg. and contain each 100 mg. of drug.
- Example II Ten g. of N-phenylbarbital is dissolved in 200 cc. of U.S.P. alcohol and to this is added with stirring 200 cc. each of glycerine, propylene glycol and polyethylene glycol 400. A few cc. of lemon extract is then added and the solution is made up to 1 liter with water.
- Example Ill Ten g. of N-phenylbarbital is dissolved in 350 cc. of U.S.P. alcohol and to this is added cc. of glycerine, 300 cc. of propylene glycol and 100 cc. of 80% cane syrup (U.S.R.). A few cc. of lemon extract are then added and the solution is made up to 1 liter with water.
- a method for the treatment of febrile convulsions which comprises the administration of N-phenylbarbital.
- a method for the treatment of febrile convulsions which comprises the administration of 3-5 mg./kg. of N-phenylbarbital.
Description
METHOD OF TREATING FEBRILE CONVULSIONS Edwin J. de Beer, Tuckahoe, N.Y., assignor to Burroughs Wellcome 8; Co. (US-A.) Inc., Tuckahoe, N.Y., a corporation of New York No Drawing. Filed June 2, 1958, Ser. No.'738,982
2 Claims. (Cl. 16765) This invention relates to a tion of febrile convulsions.
This condition occurs frequently and is especially a matter of concern in children. In susceptible individuals a rise in body temperature to levels of-about 101 -F. or somewhat higher is attended by severe convulsive seizures. The convulsive movements may cause bodily injury, severe cardiovascular damage, or even death. It is believed that these'febrile convulsions are closely related to epileptic seizures and that--a damage resulting from febrile convulsions in childhood predisposestoward 'epilepsy in later life.
Treatments available at the present time are unsatisfac tory, often being inadequate to control the convulsions and difiicult to apply. One method frequently'used is to cool the patientby means of ice packs. Another method is to place the patient under heavy-sedation'by meansof anesthetic barbiturates until lossof consciousness is'appreparation for the alleviaproached. Hospitalization is frequently required. C'ertain anticonvulsants, such as diphenylhydantoin may actually exacerbate the seizures.
-The ideal drug for use againstfebrile convulsions should not only diminish sensitivity to these seizures but should have antipyretic action. Since many barbituric acid derivatives are antipyretics a number of these were examined. Two test procedures were employed. The more fundamentals of these involves a'study of the action of drugs against spasms resulting from artificial fever in mice. Since, however, there is experimental correlation between drugs effective against epilepsy and those effective against metrazol-produced spasms, the primary screen was against metrazol spasms.
Method.Experimental seizures were induced in animals by means of pentylenetetrazol (metrazol) and the new compounds were tested for their ability to prevent all seizure activity. Metrazol was employed since the seizures produced are mainly clonic in pattern and drugs effective against such experimental seizures have been found to show some activity clinically in the treatment of petit'mal and other minor convulsive disorders.
In the preliminary screening test, doses of 10, 100, and 600 mg./kg. of each drug were administered orally to groups of mice, and anticonvulsant activity was tested at l, 2, and 3 hours after dosing. Any signs of toxicity, such as depression and incoordination, were noted.
Results.The anticonvulsant potency and toxicity of each new drug was expressed as the percentage of animals protected from the seizure and the percentage showing toxicity, within the dose range of 10 to 600 mgJkg.
'407 N -p-Anisylbarbltal tive dose,-of 422 was high'er than that 'of :Zphen'ob'ar b a1, 'trime'thadione, and 'm'ethar'bita l, and accordingly indieate's 2,955,073 Patented Oct. 4, 1960 Results were as follows:
Percentage of animals. Percentage protected Showing against Toxicity metrazol seizure B.W. Oompound Number Derivative These results show that N-phenylbarbital (B.W. No. 401) is unique in-this series of N-substituted barbitals, as a compound with marked activity against metrazol-inducedclonic seizures.
In further detailed testing, the following results were obtained:
45 mg./kg. of N-phenylbarbital protected 50 percent of mice from metrazol seizures; 2 U 5 mg./kg. protected 50 percent of mice from tonic component of the maximal electroshock seizure.
170 mg./kg. resulted in mild central nervous system excitability but the depression .which occurs with many conventional "anticonvulsants was not -observed.
Ihe protective index, or rati'ofo'f the toxic to the elfe'ca higher degree of safety.
It will be observed that of the above series of barbituric acid derivatives tested, N-phenylbarbital had a unique action different from that of even very close relatives (note Nos. 402-4). Accordingly the more fundamental test procedure was applied to this compound in comparison with drugs of known properties.
Febrile seizures were induced in mice by means of a microwave diathermy generator. In animals between 3 and 4 weeks of age, a generalized seizure response was obtained when the body temperature was raised to F. The threshold convulsive temperature was independent of the rate of temperature rise. The pattern of febrile seizure was principally clonic type. A tonic component observed at higher temperatures Was mild, spasmodic, and unsustained. Drugs were tested for their ability (1) to modify the threshold convulsive temperature (2) to abolish the seizure completely and (3) to retard the rate of rise in body temperature in the presence of hyperthermic stimulus.
As shown below, trimethadione, meprobamate and phenobarbital, of value in the treatment of petit mal and myoclonic epilepsies, were eltective in the control of febrile seizures, but large and toxic doses were required to abolish the clonns completely. Such drugs are also effective against the clonic metrazol-induced seizure. Diphenylhydantoin, which is ineffective against experimen- 3 tal metrazol seizures, and in petit mal and is used primarily for treatment of tonic major seizures, failed to control the febrile convulsion and indeed, exacerbated the clonic pattern. Acetazolamide raised the threshold convulsive temperature but did not abolish clonus completely; it was also inactive against metrazol-induced seizures.
a N-phenylbarbital proved remarkably efiective against both metrazol and fever-induced seizures. In addition, it was strongly antipyretic and its action was relatively rapid on oral administration. Compared with phenobarbital and ,metharbital, its toxicity was low and its protective therapeutic index (ratio of toxic to efiective dose) was high. a
The compound has the additional advantage of being free from toxic side-effects at doses which eifeotively protect against febrile convulsions. The side-effects which often may be observed with other compounds may be detected by the following tests: (1) the righting reflex test, (2) the positional sense test, (3) the gait stance test, (4) the muscle tone test, and (5) the equilibrium test.
Graded oral doses gave a TD of 190 mg./kg. for these neural toxicity tests. The lethal action of B.W. 401 required much higher doses. The LD was found to be 900 mg./ kg.
given to children and about twice as much to adults. The
drug may be presented in capsules, tablets or in the form of an elixir or syrup. The latter is of particular convenience in treating young children.
. Example Five hundred and thirty g. of N-phenylbarbital is ground thoroughly and sifted through a mesh sieve. It is then mixed with 116.6 g. of dried potato starch and again passed through a 60 mesh sieve. The powder is then granulated twice each time with cc. of 20 percent Feculose solution. Feculose is the tradename of a partially degraded starch preparation consisting largely of starch and high-molecular dextrins. The granules are dried over-night at F. and broken up so as to pass through a 24 mesh sieve. To this was added a mixture passed through a 60 mesh sieve of 13.25 g. of dried potato starch and 7.95 g. of stearic acid. The whole was mixed thoroughly and fed into a tabletting machine using #74 scored punches. The tablets so prepared weigh 139.5 mg. and contain each 100 mg. of drug.
Example II Ten g. of N-phenylbarbital is dissolved in 200 cc. of U.S.P. alcohol and to this is added with stirring 200 cc. each of glycerine, propylene glycol and polyethylene glycol 400. A few cc. of lemon extract is then added and the solution is made up to 1 liter with water.
Example Ill Ten g. of N-phenylbarbital is dissolved in 350 cc. of U.S.P. alcohol and to this is added cc. of glycerine, 300 cc. of propylene glycol and 100 cc. of 80% cane syrup (U.S.R.). A few cc. of lemon extract are then added and the solution is made up to 1 liter with water.
What I claim is:
1. A method for the treatment of febrile convulsions which comprises the administration of N-phenylbarbital.
2. A method for the treatment of febrile convulsions which comprises the administration of 3-5 mg./kg. of N-phenylbarbital.
References Cited in the file of this patent Bush: J. Pharmacol, vol. 68, 1940, pp. 278-283 (thru Chem. Abst, 34, 2458).
Hjort: J. Pharmacol., vol. 35, 1929, pp. -164 (thru Chem. Abst., 23, 3024).
Cecil: Textbook of Med., 7th ed., 1948, p. 28, W. B. Saunders Co;
Williams: Detoxication Mechanisms, 1947, pp. 219- 220, John Wiley and Sons, Inc., NY.
Irwin: J. Pharm..Exptl. Then, July 1958, pp. 206-211.
Daly: Staff Meeting Mayo Clinic, May 15, 1957, vol. 32, .No. 10, p. 260. a
Claims (1)
1. A METHOD FOR THE TREATMENT OF FEBRILE CONVULSIONS WHICH COMPRISES THE ADMINISTRATION OF N-PHENYLBARBITAL.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US738982A US2955073A (en) | 1958-06-02 | 1958-06-02 | Method of treating febrile convulsions |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US738982A US2955073A (en) | 1958-06-02 | 1958-06-02 | Method of treating febrile convulsions |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US2955073A true US2955073A (en) | 1960-10-04 |
Family
ID=24970310
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US738982A Expired - Lifetime US2955073A (en) | 1958-06-02 | 1958-06-02 | Method of treating febrile convulsions |
Country Status (1)
| Country | Link |
|---|---|
| US (1) | US2955073A (en) |
Cited By (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3046275A (en) * | 1958-05-30 | 1962-07-24 | Chemiewerk Homburg Zweignieder | N-substituted 2-phenyl-7-aminoalkoxy chromones |
| US3103533A (en) * | 1963-09-10 | X-trifluoro-m-tolyloxy | ||
| US3133928A (en) * | 1964-05-19 | Certificate of correction | ||
| US3153652A (en) * | 1964-10-20 | Certificate of correction | ||
| US3157573A (en) * | 1962-12-18 | 1964-11-17 | Hoffmann La Roche | Antihypertensive 3, 4-dihydro-2(1h)-isoquinolinecarboxamidine |
| US3161653A (en) * | 1960-11-23 | 1964-12-15 | Merck Ag E | 2-[(2'-methyl-benzo-thienyl-3')-methyl]-delta2-imidazoline and its pharmaceutically aceptable acid addition salts |
| US3164601A (en) * | 1959-08-01 | 1965-01-05 | Merck Ag E | Analeptically active n-substituted aminonorcamphane derivatives and their acid addition salts and quaternary ammonium compounds |
| US3167476A (en) * | 1965-01-26 | preparations acting on the central nervous | ||
| US3177209A (en) * | 1960-09-16 | 1965-04-06 | Kefalas As | Dihydroanthracene compounds |
| US3178347A (en) * | 1960-06-03 | 1965-04-13 | Bocher Gustave Marie Joseph | Psycho-equilibrating pyrrolidone carboxylic acid |
| US3183172A (en) * | 1958-02-21 | 1965-05-11 | Sandoz Ltd | Obtaining psilocybin and psilocin from fungal material |
| US3184464A (en) * | 1961-09-16 | 1965-05-18 | Boehringer & Soehne Gmbh | Tetrahydro-quinolines and tetrahydroisoquinolines |
| US3194806A (en) * | 1962-03-16 | 1965-07-13 | Troponwerke Dinklage & Co | Novel pharmacologically active quinazolinone compound |
| US3198791A (en) * | 1960-04-26 | 1965-08-03 | Hoechst Ag | New sulfanilamido-pyrazoles and process of preparing them |
| US3207766A (en) * | 1961-07-21 | 1965-09-21 | Hoechst Ag | New azido-benzenesulfonyl ureas and process for their manufacture |
| US3209025A (en) * | 1960-10-29 | 1965-09-28 | Hoechst Ag | Bis-(beta-carbhydrazido-ethyl)-sulfone |
| US3227715A (en) * | 1961-07-25 | 1966-01-04 | Knoll Ag | Benzisothiazolones |
| US3235557A (en) * | 1959-10-02 | 1966-02-15 | Aspro Nicholas Ltd | New oxazoline derivatives |
| US3250678A (en) * | 1963-01-16 | 1966-05-10 | Sterling Drug Inc | Analgesia producing benzazocines |
| US3255207A (en) * | 1962-02-09 | 1966-06-07 | Astra Ab | Quaternary ammonium salts containing anilido groups |
| US3257404A (en) * | 1962-06-15 | 1966-06-21 | Rhone Poulenc Sa | Piperazine derivatives of dibenzo[a,d] cycloheptadiene |
| US20060111743A1 (en) * | 2004-11-19 | 2006-05-25 | Gurney Harry C Jr | Method for arresting seizure activity |
-
1958
- 1958-06-02 US US738982A patent/US2955073A/en not_active Expired - Lifetime
Non-Patent Citations (1)
| Title |
|---|
| None * |
Cited By (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3103533A (en) * | 1963-09-10 | X-trifluoro-m-tolyloxy | ||
| US3133928A (en) * | 1964-05-19 | Certificate of correction | ||
| US3153652A (en) * | 1964-10-20 | Certificate of correction | ||
| US3167476A (en) * | 1965-01-26 | preparations acting on the central nervous | ||
| US3183172A (en) * | 1958-02-21 | 1965-05-11 | Sandoz Ltd | Obtaining psilocybin and psilocin from fungal material |
| US3046275A (en) * | 1958-05-30 | 1962-07-24 | Chemiewerk Homburg Zweignieder | N-substituted 2-phenyl-7-aminoalkoxy chromones |
| US3164601A (en) * | 1959-08-01 | 1965-01-05 | Merck Ag E | Analeptically active n-substituted aminonorcamphane derivatives and their acid addition salts and quaternary ammonium compounds |
| US3235557A (en) * | 1959-10-02 | 1966-02-15 | Aspro Nicholas Ltd | New oxazoline derivatives |
| US3198791A (en) * | 1960-04-26 | 1965-08-03 | Hoechst Ag | New sulfanilamido-pyrazoles and process of preparing them |
| US3178347A (en) * | 1960-06-03 | 1965-04-13 | Bocher Gustave Marie Joseph | Psycho-equilibrating pyrrolidone carboxylic acid |
| US3177209A (en) * | 1960-09-16 | 1965-04-06 | Kefalas As | Dihydroanthracene compounds |
| US3209025A (en) * | 1960-10-29 | 1965-09-28 | Hoechst Ag | Bis-(beta-carbhydrazido-ethyl)-sulfone |
| US3161653A (en) * | 1960-11-23 | 1964-12-15 | Merck Ag E | 2-[(2'-methyl-benzo-thienyl-3')-methyl]-delta2-imidazoline and its pharmaceutically aceptable acid addition salts |
| US3238101A (en) * | 1960-11-23 | 1966-03-01 | Merck Ag E | Blood vessel constricting compositions and methods of using same |
| US3207766A (en) * | 1961-07-21 | 1965-09-21 | Hoechst Ag | New azido-benzenesulfonyl ureas and process for their manufacture |
| US3227715A (en) * | 1961-07-25 | 1966-01-04 | Knoll Ag | Benzisothiazolones |
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| US3255207A (en) * | 1962-02-09 | 1966-06-07 | Astra Ab | Quaternary ammonium salts containing anilido groups |
| US3194806A (en) * | 1962-03-16 | 1965-07-13 | Troponwerke Dinklage & Co | Novel pharmacologically active quinazolinone compound |
| US3257404A (en) * | 1962-06-15 | 1966-06-21 | Rhone Poulenc Sa | Piperazine derivatives of dibenzo[a,d] cycloheptadiene |
| US3157573A (en) * | 1962-12-18 | 1964-11-17 | Hoffmann La Roche | Antihypertensive 3, 4-dihydro-2(1h)-isoquinolinecarboxamidine |
| US3250678A (en) * | 1963-01-16 | 1966-05-10 | Sterling Drug Inc | Analgesia producing benzazocines |
| US20060111743A1 (en) * | 2004-11-19 | 2006-05-25 | Gurney Harry C Jr | Method for arresting seizure activity |
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