US3773951A - Method of treating depression with 1-(2-pyridyl)piperazine - Google Patents
Method of treating depression with 1-(2-pyridyl)piperazine Download PDFInfo
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- US3773951A US3773951A US00317133A US3773951DA US3773951A US 3773951 A US3773951 A US 3773951A US 00317133 A US00317133 A US 00317133A US 3773951D A US3773951D A US 3773951DA US 3773951 A US3773951 A US 3773951A
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- pyridyl
- piperazine
- depression
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- treating depression
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- 238000000034 method Methods 0.000 title abstract description 12
- GZRKXKUVVPSREJ-UHFFFAOYSA-N pyridinylpiperazine Chemical compound C1CNCCN1C1=CC=CC=N1 GZRKXKUVVPSREJ-UHFFFAOYSA-N 0.000 title abstract description 12
- 241000124008 Mammalia Species 0.000 abstract description 4
- 239000002253 acid Substances 0.000 abstract description 4
- 150000003839 salts Chemical class 0.000 abstract description 4
- 230000000973 chemotherapeutic effect Effects 0.000 abstract description 3
- 239000003814 drug Substances 0.000 description 13
- 229940079593 drug Drugs 0.000 description 12
- 150000001875 compounds Chemical class 0.000 description 9
- 241000700159 Rattus Species 0.000 description 6
- 230000003470 muricidal effect Effects 0.000 description 6
- 239000003773 muricide Substances 0.000 description 6
- 229940126062 Compound A Drugs 0.000 description 5
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 5
- BCGWQEUPMDMJNV-UHFFFAOYSA-N imipramine Chemical compound C1CC2=CC=CC=C2N(CCCN(C)C)C2=CC=CC=C21 BCGWQEUPMDMJNV-UHFFFAOYSA-N 0.000 description 5
- 229960004801 imipramine Drugs 0.000 description 5
- SLVHMMBZOHKYBM-UHFFFAOYSA-N 1-pyridin-2-ylpiperazin-4-ium;chloride;hydrochloride Chemical compound Cl.Cl.C1CNCCN1C1=CC=CC=N1 SLVHMMBZOHKYBM-UHFFFAOYSA-N 0.000 description 4
- 208000020401 Depressive disease Diseases 0.000 description 4
- 239000000935 antidepressant agent Substances 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 201000010099 disease Diseases 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
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- 208000004547 Hallucinations Diseases 0.000 description 2
- 206010026749 Mania Diseases 0.000 description 2
- 102000010909 Monoamine Oxidase Human genes 0.000 description 2
- 108010062431 Monoamine oxidase Proteins 0.000 description 2
- 208000001089 Multiple system atrophy Diseases 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 206010031127 Orthostatic hypotension Diseases 0.000 description 2
- 239000000150 Sympathomimetic Substances 0.000 description 2
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- 206010044565 Tremor Diseases 0.000 description 2
- 229940082992 antihypertensives mao inhibitors Drugs 0.000 description 2
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- 239000002899 monoamine oxidase inhibitor Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
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- 238000010825 rotarod performance test Methods 0.000 description 2
- 229940127230 sympathomimetic drug Drugs 0.000 description 2
- 230000006794 tachycardia Effects 0.000 description 2
- 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 description 1
- 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 description 1
- ZSMRRZONCYIFNB-UHFFFAOYSA-N 6,11-dihydro-5h-benzo[b][1]benzazepine Chemical compound C1CC2=CC=CC=C2NC2=CC=CC=C12 ZSMRRZONCYIFNB-UHFFFAOYSA-N 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- 206010012239 Delusion Diseases 0.000 description 1
- HCYAFALTSJYZDH-UHFFFAOYSA-N Desimpramine Chemical compound C1CC2=CC=CC=C2N(CCCNC)C2=CC=CC=C21 HCYAFALTSJYZDH-UHFFFAOYSA-N 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 206010019851 Hepatotoxicity Diseases 0.000 description 1
- 206010022998 Irritability Diseases 0.000 description 1
- 231100000111 LD50 Toxicity 0.000 description 1
- 208000019022 Mood disease Diseases 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 206010033557 Palpitations Diseases 0.000 description 1
- 208000001431 Psychomotor Agitation Diseases 0.000 description 1
- 206010038743 Restlessness Diseases 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
- 206010043268 Tension Diseases 0.000 description 1
- 206010047513 Vision blurred Diseases 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 229960000836 amitriptyline Drugs 0.000 description 1
- KRMDCWKBEZIMAB-UHFFFAOYSA-N amitriptyline Chemical compound C1CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21 KRMDCWKBEZIMAB-UHFFFAOYSA-N 0.000 description 1
- 229940008238 amphetamine sulfate Drugs 0.000 description 1
- PYHRZPFZZDCOPH-UHFFFAOYSA-N amphetamine sulfate Chemical compound OS(O)(=O)=O.CC(N)CC1=CC=CC=C1.CC(N)CC1=CC=CC=C1 PYHRZPFZZDCOPH-UHFFFAOYSA-N 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 230000001001 anti-filiarial effect Effects 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000003001 depressive effect Effects 0.000 description 1
- 229960003914 desipramine Drugs 0.000 description 1
- -1 dimethylaminopropyl Chemical group 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 208000024732 dysthymic disease Diseases 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 201000003104 endogenous depression Diseases 0.000 description 1
- 239000003777 experimental drug Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 230000007686 hepatotoxicity Effects 0.000 description 1
- 231100000304 hepatotoxicity Toxicity 0.000 description 1
- 231100000086 high toxicity Toxicity 0.000 description 1
- CVVIJWRCGSYCMB-UHFFFAOYSA-N hydron;piperazine;dichloride Chemical compound Cl.Cl.C1CNCCN1 CVVIJWRCGSYCMB-UHFFFAOYSA-N 0.000 description 1
- 230000001505 hypomanic effect Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229960002672 isocarboxazid Drugs 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 229960001252 methamphetamine Drugs 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 210000001640 nerve ending Anatomy 0.000 description 1
- 230000001962 neuropharmacologic effect Effects 0.000 description 1
- 208000025319 neurotic depression Diseases 0.000 description 1
- 208000015238 neurotic disease Diseases 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 150000004885 piperazines Chemical class 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
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- 230000007704 transition Effects 0.000 description 1
- 229960003741 tranylcypromine Drugs 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
Definitions
- Depression is a psychiatric condition which may be diagnosed as a symptom, a syndrome, or a disease entity, depending upon the clinical situation of the patient. Although there is a lack of uniformity in classification, depression is clinically differentiated as reactive (interchangeably used with neurotic depression) or endogenous (also referred to as psychotic or involutional depression). Regardless of etiology, antidepressant drugs are a common form of therapy, and the disclosed new use of 1-(2- pyridyl)piperazine is a chemotherapeutic method of treating depression.
- Antidepressant drugs fall into three broad categories of monoamine oxidase (MAO) inhibitors, certain tricyclic compounds, and amphetamine-like drugs.
- MAO monoamine oxidase
- MAO inhibitors still in current use are isocarboxazide, nialimide, phenylzine, and tranylcypromine. Use of these compounds, however, is gradually becoming disfavored because their relatively low eflicacy is countervailed by their relatively high toxicity.
- the most dangerous toxic elfects caused by this class of drugs include hepato-toxicity, excessive central stimulation, orthostatic hypotension, and interaction with other drugs.
- More widely used in depression is a family or tricyclic compounds including imipramine, desmethylimipramine, and amitriptyline. Although these drugs are more efiective than MAO inhibitors and less toxic, they nevertheless cause a variety of untoward side eifects. Among the latter are: atropine-like effects, including dryness of the mouth, constipation, dizziness, tachycardia, palpitations, and blurred vision; various cardiovascular difficulties, including orthostatic hypotension, myocardial infarction, arrhythmias, and tachycardia; persistent tremor; and psychiatric efiects, such as a transition from depression to hypomanic or manic excitement, and hallucinations.
- atropine-like effects including dryness of the mouth, constipation, dizziness, tachycardia, palpitations, and blurred vision
- various cardiovascular difficulties including orthostatic hypotension, myocardial infarction, arrhythmias, and tachycardi
- amphetamine sulfate Although characterized as noncatecholamine sympathomimetic drugs, amphetamine sulfate, methamphetamine, and methylphenodate are effective in treating endogenous depression and the depressive phase of certain types of schizophrenia. In cases of chronic depression, tolerance is developed to the central efiects of amphetamines, and the user often increases the dose to obtain the desired elfect.
- abnormal mental conditions such as paranoid delusions and hallucinations
- central effects including restlessness, dizziness, tremor, hyperactive reflexes, irritability, insomnia, and tenseness
- gastrointestinal effects as anorexin, nausea, emesis, and diarrhea.
- antidepressant drugs refer to: Jarvik, Muray E., Drugs Used in the Treatment of Psy- 3,773,951 Patented Nov. 20, 1973 chiatric Disorders, III. Drugs for Affective Disorders (Depression and Mania), in The Pharmacological Basis of Therapeutics, 4th ed., L. S. Goodman and A. Gilman, editors, New York, Macmillan, 1970, chapter 12, pp. 181- 192; and Innes, Ian R. and Nickerson, Mark, Drugs Acting on Postganglionic Andrenergic Nerve Endings and Structures Innervated by Them (Sympathomimetic Drugs), H. Noncatecholamines, op. cit., chapter 24, pp. 500-520.
- the compound 1-(2-pyridyl)piperazine is not related to the drugs described above and has the following structural formula:
- 1-(2-pyridyl)piperazine The synthesis of 1-(2-pyridyl)piperazine is described by Hamlin et al. in J. Am. Chem. Soc. 71:2731-2743 (1949) and by Howard et al. in J. Org. Chem., 18:1484-1488 (1953). In the publication by Howard, 1-(2-pyridyl)piperazine was reported to have no analgesic or antifilarial activity. Although L. W. Roth in I. Pharmac. Exp. Ther., 110: 157-165 (1954) reported the pharmacological activity of a series of substituted piperazines, 1-(2-pyridyl piperazine was not tested.
- the essential feature of this discovery is the utility of 1 (2 pyridyl)piperazine (hereinafter called compound A for convenience) in the treatment of depression as a symptom, syndrome, or a disease entity.
- Administration of an eflective amount of compound A generally in daily doses of from 2 mg./kg. to 60 mg./kg., produces an antidepressant effect in experimental animals.
- Pharmaceutically acceptable acid addition salts of compound A can be used in lieu of the parent compound.
- compound A exhibits greater eflicacy than the reference drug.
- Dose forms of compound A can be conveniently prepared by the addition of pharmaceutically acceptable vehicles generally used in formulations. Dose forms can be prepared in. a solid or liquid state by methods known in the art for oral, intravenous, parenteral, intramuscular, and subcutaneous administration.
- Example 1 The method of treating depression by administering 1- (2-pyridyl)piperazine to rats in an experimental model of depression is assessed according to the procedure developed by Horovitz et al., described in Int. J. NeuropharmacoL, 5:405-411 (1966). The basis of this procedure is the neuropharmacological effect of antidepressant drugs in suppressing the spontaneous killing of mice (muricide) by selective killer rats. This muricide test has gained wide recognition among neuropharmacologists to test compounds for treating depression.
- Example 2 Because depression of the muricide response may be symptomatic of motor impairment, the method of treating depression by administering 1 (2 pyridyl)piperazine dihydrochloride was also evaluated by the rotarod test of Dunham and Miya described in I. Am. Pharm. Assoc. (sci. ed.), 46:208-209 (1957). In this test, rats are trained to walk for periods of 100 seconds on a wooden rod rotating at 13 r.p.m. After intraperitoneal administration of a drug walking times are recorded at zero time and at various 15 minute intervals afterwards.
- Table II summarizes the result of the rotarod test for 1 (2 pyridyl)piperazine dihydrochloride and the reference drug imipramine.
- the specificity of the anti-muricidal eifect is measured by calculating the ratio of the rotarod ED to the anti muricide ED A ratio significantly greater than 1 indicates a specific anti-muricidal effect at non-debilitating doses.
- the ratio of rotarod ED to antimuricidal ED for 1 (2 pyridyl)piperazine dihydrochloride is 16.4, substantially in excess of unity, whereas the respective ratio for imipramine is 1.5.
- the median lethal dose (LD in mg./kg.) for 1-(2- pyridyl) piperazine dihydrochloride in rats is 681 mg./ kg.
- a method of treating a mammal having a symptom, a syndrome or a disease entity characterized as depression which comprises:
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- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
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Abstract
ADMINISTRATION OF 1-(2-PYRIDYL)PIPERAZINE OR A PHARMACEUTICALLY ACCEPTABLE ACID ADDITION SALT THEREOF IS DISCLOSED AS A CHEMOTHERAPEUTIC METHOD OF TREATING MANIFESTATIONS OF DEPRESSION IN EXPERIMENTAL MAMMALS. DAILY DOSES RANGING FROM 2 MG./KG. TO 60 MG./KG. PER DAY ARE CONSIDERED EFFECTIVE.
Description
United States Patent 3,773,951 METHOD OF TREATING DEPRESSION WITH 1-(2-PYRIDYL)PIPERAZINE Rodolfo Rodriguez, Mexico City, Mexico, assiguor to Miles Laboratories, Inc., Elkhart, Ind. No Drawing. Filed Dec. 21, 1972, Ser. No. 317,133 Int. Cl. A61k 27/00 US. Cl. 424-250 2 Claims ABSTRACT OF THE DISCLOSURE Administration of 1-(2-pyridyl)piperazine or a pharmaceutically acceptable acid addition salt thereof is disclosed as a chemotherapeutic method of treating manifestations of depression in experimental mammals. Daily doses ranging from 2 mg./kg. to 60 mg./kg. per day are considered effective.
BACKGROUND OF THE INVENTION Field of the invention Depression is a psychiatric condition which may be diagnosed as a symptom, a syndrome, or a disease entity, depending upon the clinical situation of the patient. Although there is a lack of uniformity in classification, depression is clinically differentiated as reactive (interchangeably used with neurotic depression) or endogenous (also referred to as psychotic or involutional depression). Regardless of etiology, antidepressant drugs are a common form of therapy, and the disclosed new use of 1-(2- pyridyl)piperazine is a chemotherapeutic method of treating depression.
DESCRIPTION OF THE PRIOR ART Antidepressant drugs fall into three broad categories of monoamine oxidase (MAO) inhibitors, certain tricyclic compounds, and amphetamine-like drugs.
Among MAO inhibitors still in current use are isocarboxazide, nialimide, phenylzine, and tranylcypromine. Use of these compounds, however, is gradually becoming disfavored because their relatively low eflicacy is countervailed by their relatively high toxicity. The most dangerous toxic elfects caused by this class of drugs include hepato-toxicity, excessive central stimulation, orthostatic hypotension, and interaction with other drugs.
More widely used in depression is a family or tricyclic compounds including imipramine, desmethylimipramine, and amitriptyline. Although these drugs are more efiective than MAO inhibitors and less toxic, they nevertheless cause a variety of untoward side eifects. Among the latter are: atropine-like effects, including dryness of the mouth, constipation, dizziness, tachycardia, palpitations, and blurred vision; various cardiovascular difficulties, including orthostatic hypotension, myocardial infarction, arrhythmias, and tachycardia; persistent tremor; and psychiatric efiects, such as a transition from depression to hypomanic or manic excitement, and hallucinations.
Although characterized as noncatecholamine sympathomimetic drugs, amphetamine sulfate, methamphetamine, and methylphenodate are effective in treating endogenous depression and the depressive phase of certain types of schizophrenia. In cases of chronic depression, tolerance is developed to the central efiects of amphetamines, and the user often increases the dose to obtain the desired elfect. Among other undesirable features are: abnormal mental conditions such as paranoid delusions and hallucinations; central effects, including restlessness, dizziness, tremor, hyperactive reflexes, irritability, insomnia, and tenseness; and gastrointestinal effects, as anorexin, nausea, emesis, and diarrhea.
For a discussion of antidepressant drugs, refer to: Jarvik, Muray E., Drugs Used in the Treatment of Psy- 3,773,951 Patented Nov. 20, 1973 chiatric Disorders, III. Drugs for Affective Disorders (Depression and Mania), in The Pharmacological Basis of Therapeutics, 4th ed., L. S. Goodman and A. Gilman, editors, New York, Macmillan, 1970, chapter 12, pp. 181- 192; and Innes, Ian R. and Nickerson, Mark, Drugs Acting on Postganglionic Andrenergic Nerve Endings and Structures Innervated by Them (Sympathomimetic Drugs), H. Noncatecholamines, op. cit., chapter 24, pp. 500-520.
The compound 1-(2-pyridyl)piperazine is not related to the drugs described above and has the following structural formula:
The synthesis of 1-(2-pyridyl)piperazine is described by Hamlin et al. in J. Am. Chem. Soc. 71:2731-2743 (1949) and by Howard et al. in J. Org. Chem., 18:1484-1488 (1953). In the publication by Howard, 1-(2-pyridyl)piperazine was reported to have no analgesic or antifilarial activity. Although L. W. Roth in I. Pharmac. Exp. Ther., 110: 157-165 (1954) reported the pharmacological activity of a series of substituted piperazines, 1-(2-pyridyl piperazine was not tested.
SUMMARY OF THE INVENTION The essential feature of this discovery is the utility of 1 (2 pyridyl)piperazine (hereinafter called compound A for convenience) in the treatment of depression as a symptom, syndrome, or a disease entity. Administration of an eflective amount of compound A, generally in daily doses of from 2 mg./kg. to 60 mg./kg., produces an antidepressant effect in experimental animals. Pharmaceutically acceptable acid addition salts of compound A can be used in lieu of the parent compound. In comparative tests with imipramine as a reference, compound A exhibits greater eflicacy than the reference drug.
Dose forms of compound A can be conveniently prepared by the addition of pharmaceutically acceptable vehicles generally used in formulations. Dose forms can be prepared in. a solid or liquid state by methods known in the art for oral, intravenous, parenteral, intramuscular, and subcutaneous administration.
DESCRIPTION OF THE PREFERRED EMBODIMENTS Example 1 The method of treating depression by administering 1- (2-pyridyl)piperazine to rats in an experimental model of depression is assessed according to the procedure developed by Horovitz et al., described in Int. J. NeuropharmacoL, 5:405-411 (1966). The basis of this procedure is the neuropharmacological effect of antidepressant drugs in suppressing the spontaneous killing of mice (muricide) by selective killer rats. This muricide test has gained wide recognition among neuropharmacologists to test compounds for treating depression.
Killer rats of both sexes are easily ascertained as those which kill mice consistently within 5 seconds after confrontation. Experimental drugs are tested by observation of muricide responses at 15 minute intervals after intraperitoneal administration of the drugs. Table I summ'arizes the results of the muricide test for 1 (2- pyridyl)piperazine dihydrocbloride and a reference compound, imipramine, 5 (3 dimethylaminopropyl) 10,11- dihydro 5H dibenz[b,f]azepine (US. Pat. No. 2,554,736, 1951). The median'effective dose and confidence limits are represented by the standard abbreviations ED and C1 respectively. The number of rats observed is indicated under the column N.
Example 2 Because depression of the muricide response may be symptomatic of motor impairment, the method of treating depression by administering 1 (2 pyridyl)piperazine dihydrochloride was also evaluated by the rotarod test of Dunham and Miya described in I. Am. Pharm. Assoc. (sci. ed.), 46:208-209 (1957). In this test, rats are trained to walk for periods of 100 seconds on a wooden rod rotating at 13 r.p.m. After intraperitoneal administration of a drug walking times are recorded at zero time and at various 15 minute intervals afterwards.
Table II summarizes the result of the rotarod test for 1 (2 pyridyl)piperazine dihydrochloride and the reference drug imipramine.
The specificity of the anti-muricidal eifect is measured by calculating the ratio of the rotarod ED to the anti muricide ED A ratio significantly greater than 1 indicates a specific anti-muricidal effect at non-debilitating doses. The ratio of rotarod ED to antimuricidal ED for 1 (2 pyridyl)piperazine dihydrochloride is 16.4, substantially in excess of unity, whereas the respective ratio for imipramine is 1.5.
The median lethal dose (LD in mg./kg.) for 1-(2- pyridyl) piperazine dihydrochloride in rats is 681 mg./ kg.
What is claimed is:
1. A method of treating a mammal having a symptom, a syndrome or a disease entity characterized as depression, which comprises:
administering to said mammal an effective amount of a compound selected from the group consisting essentially of 1 (2 pyridyl)piperazine and a pharmaceutically acceptable acid addition salt thereof.
2. A method as in claim 1, wherein said compound is 1-(2-pyridy1)piperazine dihydrochloride.
References Cited UNITED STATES PATENTS 2,606,906 8/1952 Hultquist 260-268 2,958,694 11/1960 Ianssen 424-250 STANLEY J. FRIEDMAN, Primary Examiner
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US31713372A | 1972-12-21 | 1972-12-21 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3773951A true US3773951A (en) | 1973-11-20 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US00317133A Expired - Lifetime US3773951A (en) | 1972-12-21 | 1972-12-21 | Method of treating depression with 1-(2-pyridyl)piperazine |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4078063A (en) * | 1976-09-24 | 1978-03-07 | Merck & Co., Inc. | Piperazinylpyridines |
| EP0065757A1 (en) * | 1981-05-26 | 1982-12-01 | Merck & Co. Inc. | 1-(3-Halo-2-pyridinyl)piperazines, processes for their preparation and pharmaceutical composition containing them |
| US4381302A (en) * | 1981-05-26 | 1983-04-26 | Merck & Co., Inc. | (6aα,10aα,11aα)-2-(2-Pyridinyl)-1,3,4,6,6a,7,8,9,10,10a,11,11a-dodecahydro-2H-pyrazino]1,2-b]isoquinoline and derivatives |
| US4442103A (en) * | 1981-05-26 | 1984-04-10 | Merck & Co., Inc. | Treating sedation with 1-(3-substituted-2-pyridinyl) piperazines |
| US4456604A (en) * | 1981-05-26 | 1984-06-26 | Merck & Co., Inc. | 1-(3-Halo-2-pyridinyl) piperazine |
| US4876256A (en) * | 1988-04-29 | 1989-10-24 | Merck & Co., Inc. | Alkylpiperazinylpyridines as hypoglycemic agents |
-
1972
- 1972-12-21 US US00317133A patent/US3773951A/en not_active Expired - Lifetime
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4078063A (en) * | 1976-09-24 | 1978-03-07 | Merck & Co., Inc. | Piperazinylpyridines |
| FR2365567A1 (en) * | 1976-09-24 | 1978-04-21 | Merck & Co Inc | NEW PIPERAZINYLPYRIDINES USEFUL AS MEDICINAL PRODUCTS |
| EP0065757A1 (en) * | 1981-05-26 | 1982-12-01 | Merck & Co. Inc. | 1-(3-Halo-2-pyridinyl)piperazines, processes for their preparation and pharmaceutical composition containing them |
| US4381302A (en) * | 1981-05-26 | 1983-04-26 | Merck & Co., Inc. | (6aα,10aα,11aα)-2-(2-Pyridinyl)-1,3,4,6,6a,7,8,9,10,10a,11,11a-dodecahydro-2H-pyrazino]1,2-b]isoquinoline and derivatives |
| US4442103A (en) * | 1981-05-26 | 1984-04-10 | Merck & Co., Inc. | Treating sedation with 1-(3-substituted-2-pyridinyl) piperazines |
| US4456604A (en) * | 1981-05-26 | 1984-06-26 | Merck & Co., Inc. | 1-(3-Halo-2-pyridinyl) piperazine |
| US4876256A (en) * | 1988-04-29 | 1989-10-24 | Merck & Co., Inc. | Alkylpiperazinylpyridines as hypoglycemic agents |
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