US3023146A - 2-propionyl-10[gamma-(n'-beta-hydroxyethyl piperazino)-propyl]-phenothiazine: processfor the treatment of withdrawn psychotic subjects - Google Patents
2-propionyl-10[gamma-(n'-beta-hydroxyethyl piperazino)-propyl]-phenothiazine: processfor the treatment of withdrawn psychotic subjects Download PDFInfo
- Publication number
- US3023146A US3023146A US33894A US3389460A US3023146A US 3023146 A US3023146 A US 3023146A US 33894 A US33894 A US 33894A US 3389460 A US3389460 A US 3389460A US 3023146 A US3023146 A US 3023146A
- Authority
- US
- United States
- Prior art keywords
- phenothiazine
- propyl
- propionyl
- withdrawn
- treatment
- 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
- 208000028017 Psychotic disease Diseases 0.000 title claims description 9
- 229950000688 phenothiazine Drugs 0.000 title claims description 9
- 238000000034 method Methods 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 9
- 239000000203 mixture Substances 0.000 claims description 6
- WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 claims description 5
- 230000001684 chronic effect Effects 0.000 claims description 4
- 230000001225 therapeutic effect Effects 0.000 claims description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- -1 alkyl radical Chemical class 0.000 description 6
- 206010007776 catatonia Diseases 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 150000002990 phenothiazines Chemical class 0.000 description 5
- NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical group C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000012736 aqueous medium Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N formaldehyde Natural products O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000002936 tranquilizing effect Effects 0.000 description 2
- PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- XPGPHJNCOZQFAU-UHFFFAOYSA-N 1-(10h-phenothiazin-2-yl)propan-1-one Chemical compound C1=CC=C2NC3=CC(C(=O)CC)=CC=C3SC2=C1 XPGPHJNCOZQFAU-UHFFFAOYSA-N 0.000 description 1
- 206010002942 Apathy Diseases 0.000 description 1
- QZXATCCPQKOEIH-UHFFFAOYSA-N Florasulam Chemical compound N=1N2C(OC)=NC=C(F)C2=NC=1S(=O)(=O)NC1=C(F)C=CC=C1F QZXATCCPQKOEIH-UHFFFAOYSA-N 0.000 description 1
- MFESCIUQSIBMSM-UHFFFAOYSA-N I-BCP Chemical compound ClCCCBr MFESCIUQSIBMSM-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- OCBFFGCSTGGPSQ-UHFFFAOYSA-N [CH2]CC Chemical compound [CH2]CC OCBFFGCSTGGPSQ-UHFFFAOYSA-N 0.000 description 1
- 238000010669 acid-base reaction Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- CODNYICXDISAEA-UHFFFAOYSA-N bromine monochloride Chemical compound BrCl CODNYICXDISAEA-UHFFFAOYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 230000002903 catalepsic effect Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- RUZYUOTYCVRMRZ-UHFFFAOYSA-N doxazosin Chemical compound C1OC2=CC=CC=C2OC1C(=O)N(CC1)CCN1C1=NC(N)=C(C=C(C(OC)=C2)OC)C2=N1 RUZYUOTYCVRMRZ-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 235000019256 formaldehyde Nutrition 0.000 description 1
- 229960004279 formaldehyde Drugs 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 229940025708 injectable product Drugs 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000012439 solid excipient Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 229940066767 systemic antihistamines phenothiazine derivative Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D279/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C07D279/10—1,4-Thiazines; Hydrogenated 1,4-thiazines
- C07D279/14—1,4-Thiazines; Hydrogenated 1,4-thiazines condensed with carbocyclic rings or ring systems
- C07D279/18—[b, e]-condensed with two six-membered rings
- C07D279/22—[b, e]-condensed with two six-membered rings with carbon atoms directly attached to the ring nitrogen atom
- C07D279/24—[b, e]-condensed with two six-membered rings with carbon atoms directly attached to the ring nitrogen atom with hydrocarbon radicals, substituted by amino radicals, attached to the ring nitrogen atom
- C07D279/28—[b, e]-condensed with two six-membered rings with carbon atoms directly attached to the ring nitrogen atom with hydrocarbon radicals, substituted by amino radicals, attached to the ring nitrogen atom with other substituents attached to the ring system
Definitions
- Phenothiazine compounds have been extensively investigated both pharmacologically and clinically and in general a substantial number have been found to possess a tranquilizing or sedative action, particularly on agitated psychotics. Moreover, a few of these compounds have demonstrated the ability not only to calm the violent patient but to go still further, in the direction of produc ing a catatonic or cataleptic state. In some circumstances, the latter may be a desirable property.
- the present invention involves the discovery of new compounds of the phenothiazine class that have the ability to act on the central nervous system and are specifically useful for the treatment of psychotics. These may be illustrated by the general formula wherein R represents a lower alkyl, preferably ethyl, while R represents a hydroxy substituted lower alkyl radical, and preferably a beta-hydroxyethyl radical.
- R represents a lower alkyl, preferably ethyl
- R represents a hydroxy substituted lower alkyl radical, and preferably a beta-hydroxyethyl radical.
- the pharmaceutically acceptable acid-addition salts are also contemplated as falling within the scope of the invention.
- Various acids may be used that will form acceptable non-toxic acid-addition salts at the therapeutic level, as for example, phosphoric, sulfuric,
- the compounds of the invention may be used either orally or parenterally.
- parenteral inject-ions a unit dosage range" of 5 to 15 mg./cc. is useful, and preferably a unit dosage of not more than about 10 milligrams of active material per cc.
- the free base may be utilized in suppository compositions but when an oral or injectable composition is contemplated, the active ingredient is utilized in the form of an acid-addition salt.
- the dosage may range from 10 to 400 mg./day depending on the extent of the disease. Simple dosage units ranging from 10 mg. to mg. are practical. While tablets are preferred, one may also make use of capsules or suspensions. In the latter case, it would be necessary to select a salt that is sparingly water soluble.
- the active ingredient is incorporated on a carrier which could be the usual well-known excipients.
- various well-known suspending agents as for example, carboxy' methyl cellulose should be used.
- an injectable preparation When considering an injectable preparation, this may be made up in dry form which may be reconstituted for immediate use, or an injectable product may be prepared in the usual way, utilizing an isotonic medium.
- an acid-addition salt when utilized in an aqueous medium, when the product is not intended to be utilized immediately, it must be buffered and stabilized since phenothiazines are unstable in an aqueous medium.
- phenothiazines are unstable in an aqueous medium.
- phenothiazines are unstable in an aqueous medium.
- useful substances are ascorbic acid or sodium form aldehyde sul- 3 foxylate or sodium metabisuliite or combinations of these.
- Preservatives are also utilized in many compositions and illustrative, of these may be mentioned the parabens,
- Weclaimz H The method of treating achronic psychotic person who exhibits regression predominantly characterized by symptoms of withdrawal and apathy which comprises, administering to such person atherapentic composition oontaining a phenothiazine of the group eonsistingoi 2- ropi ny -ltH'r-(N-fi vd v hvl pip z l n pynphenothiazine and pharmaceutically acceptable acid addition salts thereof, combined with a carrier, said phenothiazine being present in an amount from about 5 to 100 milligrams per dosage unit.
- composition comprises a solid excipient carrier.
Description
United States Patent 3,023,146 2-PROPIONYL-10[ -(N'-/3-HYDROXYETHYL PIPER- AZINO) PROPYL] PHENQTHIAZINE: PROCESS FOR THE TREATMENT OF WITHDRAWN PSY- CHOTIC SUBJECTS Richard F. Tislow, Philadelphia, William F. Bruce, Havertown, and James A. Page, Bel-Wyn, Pa., assignors to American Home Products Corporation, New York, N.Y., a corporation of Delaware No Drawing. Filed June 6, 1960, Ser. No. 33,894 4 Claims. (Cl. 16765) This invention relates to phenothiazine derivatives and more particularly. to acylated phenothiazines having useful therapeutic activity.
Phenothiazine compounds have been extensively investigated both pharmacologically and clinically and in general a substantial number have been found to possess a tranquilizing or sedative action, particularly on agitated psychotics. Moreover, a few of these compounds have demonstrated the ability not only to calm the violent patient but to go still further, in the direction of produc ing a catatonic or cataleptic state. In some circumstances, the latter may be a desirable property.
However, the ability to supress agitation is not invariably desired or useful. It is recognized that there is a large reservoir of mentally ill presons who are not actively violent or agitated. In the case of frank schizophrenia, for example, after a period of time the manifestations are likely to have moved through the agitated stage to a vegetative or catatonic stage. In this latter stage one would not require or seek a tranquilizing or catatonic action in a drug. What is needed is a drug capable of arousing or awakening the patient from the withdrawn or catatonic state.
The present invention involves the discovery of new compounds of the phenothiazine class that have the ability to act on the central nervous system and are specifically useful for the treatment of psychotics. These may be illustrated by the general formula wherein R represents a lower alkyl, preferably ethyl, while R represents a hydroxy substituted lower alkyl radical, and preferably a beta-hydroxyethyl radical. Thus, a compound which has been found to possess an unusual ability to arouse emotionally regressed patients that appear to be in a catatonic state is 2-propionyl-10-[' -(N e-hydroxyethyl piperazino)-propyl]-phenothiazine.
y In addition to the basic compounds illustrated by the above formula, the pharmaceutically acceptable acid-addition salts are also contemplated as falling within the scope of the invention. Various acids may be used that will form acceptable non-toxic acid-addition salts at the therapeutic level, as for example, phosphoric, sulfuric,
- chlorobromide.
not is alkylated with an alkylene halide, such as trimethyl-' ene chlorobromide. Following the alkylation step, the reaction product is then treated with the N-substituted piperazino compound and the final basic desired compound is isolated. This method is described in the application of Kantor and Tubis, Serial No. 612,881, filed Sept. 28, 1956. To prepare an acid-addition salt, one may use any known procedure, as for example, a simple acid-base reaction carried out in an organic solvent.
The following example more specifically teaches the process of preparation but it is to be understood that the example is'merely to be taken as illustrative and not limitative of the invention.
Exaniple In a round-bottomed flask were placed 35 grams of 2- propionyl phenothiazine (0.14 m.), 7 grams of 50% sodium hydride in mineral oil (0.14 m.), and 240 cc. of dimethyl formamide dried over sodium hydride. The resultant solution was stirred at room temperature for 2 hours, and then 88 grams (0.56 m.) of trimethylene chlorobromide was added at once.
The mixture was stirred for 2 hours, heated at 6070 C. for 1 hour and poured into 2 liters of H 0. The resulting suspension was extracted with ether, the ether layer separated and the ether removed under vacuum. A gummy mass remained which was dissolved in decalin and the solution was partly distilled to remove excess After removal of most of the decalin under vacuum, the residue was treated with a large excess of N-(B-hydroxyethyl)-piperazine and heated on a steam bath for 2 hours. This material was extracted with dilute aqueous l-lCl, this acid layer neutralized with aqueous base and the resulting oil extracted into ether. The ether layer was washed with water until the washings were neutral and dried over anhydrous potassium carbonate. On treatment with maleic acid in ether :1 yellow solid separated which was recrystallized from isopropanol. This yellow solid had MP. =l-177 C.
C H O N S Cale. 8:49, 0:584, H=6.0. Found: S=4.7, C=58.6, H=6.6.
The compounds of the invention may be used either orally or parenterally. For parenteral inject-ions a unit dosage range" of 5 to 15 mg./cc. is useful, and preferably a unit dosage of not more than about 10 milligrams of active material per cc. The free base may be utilized in suppository compositions but when an oral or injectable composition is contemplated, the active ingredient is utilized in the form of an acid-addition salt. As an oral medicinal, the dosage may range from 10 to 400 mg./day depending on the extent of the disease. Simple dosage units ranging from 10 mg. to mg. are practical. While tablets are preferred, one may also make use of capsules or suspensions. In the latter case, it would be necessary to select a salt that is sparingly water soluble. In the dry form, the active ingredient is incorporated on a carrier which could be the usual well-known excipients. In the case of an aqueous suspension, various well-known suspending agents, as for example, carboxy' methyl cellulose should be used.
When considering an injectable preparation, this may be made up in dry form which may be reconstituted for immediate use, or an injectable product may be prepared in the usual way, utilizing an isotonic medium. It should be pointed out that where an acid-addition salt is utilized in an aqueous medium, when the product is not intended to be utilized immediately, it must be buffered and stabilized since phenothiazines are unstable in an aqueous medium. For bufiering, one could use, for example, sodium acetate and acetic acid or sodium citrate with citric acid. As stabilizers or antioxidants, useful substances are ascorbic acid or sodium form aldehyde sul- 3 foxylate or sodium metabisuliite or combinations of these. Preservatives are also utilized in many compositions and illustrative, of these may be mentioned the parabens,
phenolor sodium benzoate, among the well-known antibacterial and antifungal agents. g
7' This application is a continuation-in-part of our application Serial No. 817,740, filed June 3, 1959.
Weclaimz H The method of treating achronic psychotic person who exhibits regression predominantly characterized by symptoms of withdrawal and apathy which comprises, administering to such person atherapentic composition oontaining a phenothiazine of the group eonsistingoi 2- ropi ny -ltH'r-(N-fi vd v hvl pip z l n pynphenothiazine and pharmaceutically acceptable acid addition salts thereof, combined with a carrier, said phenothiazine being present in an amount from about 5 to 100 milligrams per dosage unit.
2. The method of treating a chronic psychotic as described in claim 1; wherein the phenothiazine compound is in the form of a non-toxic acid-addition salt and the carrier comprises an aqueous vehicle.
3. The method of treating a chronic psychotic as described in claim. 2; wherein the phenothiazine compound is present in an ameum'nom about 5 to 15 mg./cc.,
14. The method of treating a chronic psychotic as described in claim. 1; wherein the composition comprises a solid excipient carrier.
cannot et a1. Aug. 4,11959 Gulesich et a1. Mar. 1S, 1960
Claims (1)
1. THE METHOD OF TREATING A CHRONIC PSYCHOTIC PERSON WHO EXHIBITS REGRESSION PREDOMINANTLY CHARACTERIZED BY SYMPTOMS OF WITHDRAWAL AND APATHY WHICH COMPRISES, ADMINISTERING TO SUCH PERSON A THERAPEUTIC COMPOSITION CONTAINING A PHENOTHIAZINE OF THE GROUP CONSISTING OF 2PROPIONYL-10-(Y-(N''-B-HYDROXYETHYL PIPERAZINO) -PROPYL)PHENOTHIAZINE AND PHARMACEUTICALLY ACCEPTABLE ACID-ADDITION SALTS THEREOF, COMBINED WITH A CARRIER, SAID PHENOTHIAZINE BEING PRESENT IN AN AMOUNT FROM ABOUT 5 TO 100 MILLIGRAMS PER DOSAGE UNIT.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US33894A US3023146A (en) | 1960-06-06 | 1960-06-06 | 2-propionyl-10[gamma-(n'-beta-hydroxyethyl piperazino)-propyl]-phenothiazine: processfor the treatment of withdrawn psychotic subjects |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US33894A US3023146A (en) | 1960-06-06 | 1960-06-06 | 2-propionyl-10[gamma-(n'-beta-hydroxyethyl piperazino)-propyl]-phenothiazine: processfor the treatment of withdrawn psychotic subjects |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3023146A true US3023146A (en) | 1962-02-27 |
Family
ID=21873076
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US33894A Expired - Lifetime US3023146A (en) | 1960-06-06 | 1960-06-06 | 2-propionyl-10[gamma-(n'-beta-hydroxyethyl piperazino)-propyl]-phenothiazine: processfor the treatment of withdrawn psychotic subjects |
Country Status (1)
| Country | Link |
|---|---|
| US (1) | US3023146A (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3218232A (en) * | 1962-11-09 | 1965-11-16 | American Home Prod | Method for relieving depression and composition therefor |
| US3305547A (en) * | 1961-11-25 | 1967-02-21 | Boehringer & Soehne Gmbh | Alkoxypiperidine derivatives and their salts |
| US3317385A (en) * | 1967-05-02 | Method of treatment of depression in mammals | ||
| US3520885A (en) * | 1965-10-12 | 1970-07-21 | Robins Co Inc A H | Phenothiazine salts |
| US3885034A (en) * | 1955-09-07 | 1975-05-20 | Bayer Ag | Phenothiazine derivatives in the treatment of psychotic persons |
| US11588214B2 (en) | 2017-01-27 | 2023-02-21 | Cps Technology Holdings Llc | Battery straps |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2898336A (en) * | 1957-04-11 | 1959-08-04 | Rhone Poulenc Sa | Phenthiazine derivatives |
| US2928767A (en) * | 1957-07-17 | 1960-03-15 | Smith Kline French Lab | Stabilized phenothiazine preparations |
-
1960
- 1960-06-06 US US33894A patent/US3023146A/en not_active Expired - Lifetime
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2898336A (en) * | 1957-04-11 | 1959-08-04 | Rhone Poulenc Sa | Phenthiazine derivatives |
| US2928767A (en) * | 1957-07-17 | 1960-03-15 | Smith Kline French Lab | Stabilized phenothiazine preparations |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3317385A (en) * | 1967-05-02 | Method of treatment of depression in mammals | ||
| US3885034A (en) * | 1955-09-07 | 1975-05-20 | Bayer Ag | Phenothiazine derivatives in the treatment of psychotic persons |
| US3305547A (en) * | 1961-11-25 | 1967-02-21 | Boehringer & Soehne Gmbh | Alkoxypiperidine derivatives and their salts |
| US3218232A (en) * | 1962-11-09 | 1965-11-16 | American Home Prod | Method for relieving depression and composition therefor |
| US3520885A (en) * | 1965-10-12 | 1970-07-21 | Robins Co Inc A H | Phenothiazine salts |
| US11588214B2 (en) | 2017-01-27 | 2023-02-21 | Cps Technology Holdings Llc | Battery straps |
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