US3439096A - Method of improving microcirculation and treating senility with beta-(pyridyl lower alkyl)-amines - Google Patents
Method of improving microcirculation and treating senility with beta-(pyridyl lower alkyl)-amines Download PDFInfo
- Publication number
- US3439096A US3439096A US486237A US3439096DA US3439096A US 3439096 A US3439096 A US 3439096A US 486237 A US486237 A US 486237A US 3439096D A US3439096D A US 3439096DA US 3439096 A US3439096 A US 3439096A
- Authority
- US
- United States
- Prior art keywords
- pyridyl
- lower alkyl
- microcirculation
- amines
- amine
- 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
- 230000004089 microcirculation Effects 0.000 title description 24
- 125000000217 alkyl group Chemical group 0.000 title description 20
- 238000000034 method Methods 0.000 title description 17
- 206010039966 Senile dementia Diseases 0.000 description 15
- 230000001771 impaired effect Effects 0.000 description 13
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 12
- 239000002253 acid Substances 0.000 description 12
- 231100000252 nontoxic Toxicity 0.000 description 12
- 230000003000 nontoxic effect Effects 0.000 description 12
- 150000003839 salts Chemical class 0.000 description 12
- 238000011282 treatment Methods 0.000 description 8
- 229960001340 histamine Drugs 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 3
- -1 pyridyl alkyl amines Chemical class 0.000 description 3
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 230000006978 adaptation Effects 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 239000000902 placebo Substances 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 208000031104 Arterial Occlusive disease Diseases 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 206010058990 Venous occlusion Diseases 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 208000021328 arterial occlusion Diseases 0.000 description 1
- 230000036770 blood supply Effects 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- XHFGWHUWQXTGAT-UHFFFAOYSA-N n-methylpropan-2-amine Chemical compound CNC(C)C XHFGWHUWQXTGAT-UHFFFAOYSA-N 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 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
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 239000005526 vasoconstrictor agent Substances 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/38—Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
Definitions
- This invention relates to the improving of microcirculation and to the treatment of senility, and more partiularly to oral treatments to treat microcirculation and senility, according to which invention a beta-(2-pyridyllower alyl)-amine is administered in order to achieve these results.
- the microcirculatory or microvascular system is generally described as consisting of all vessels with an internal diameter of 100 microns or less. It is possible by microscopy, but not by the naked eye, to see the characteristics of capillary circulation or microcirculation. The tiny vessels through which microcirculation takes place are really only endothelial tubes with no powers of contraction.
- microv-ascular system accounts for the failure of tissue or organ function in a variety of common clinical conditions.
- the microcirculation may be comprised by either arterial occlusions or venous occlusions. In both cases the capillary network immediately ahead or behind the plug will be blocked. Vast numbers of capillary vessels may be obstructed to involve almost an entire organ, and yet central or large vessel flow may give no indication of this.
- impaired microcirculation is to a great extent mediated by histamine.
- Induced histamine is believed to be newly synthesized in free, pharmacologically active form, in or near the vascular endothelial cells.
- histamine can only be administered by injection, and in addition, the dosages of histamine must be very carefully regulated because overdosages of histamine are highly toxic and may be fatal.
- the present invention mainly comprises a method of improving impaired microcirculation by administration of a compound selected from the group consisting of )8-(2-pyridyl lower alkyl)-amines, B-(4-pyridyl lower alkyl)-amines and nontoxic acid addition salts thereof.
- the administration of the 8-(2- or 4-pyridyl lower alkyl)-amines, or their non-toxic acid addition salts is preferably effected orally using a rnicrocirculation-improving effective amount thereof.
- the lower alkyl portion of the pyridyl alkyl amines of the invention may be any alkyl of up to 5 carbon atoms.
- the most preferred alkyl groups are methyl and ethyl.
- the most preferred compounds are B-(2-pyridyl)- ethyl methyl amine, fl-(4-pyridyl)-ethyl methyl amine, l-(2-pyridyl)2methyl amino propane, and non-toxic acid addition salts thereof such as the hydrochloride, the tartrate, the fumarate, the gluconate, etc.
- the 3-(2- or 4-pyridyl alkyl)-amines of the present invention may be administered in amounts as low as 0.5 mg. per day and as high as 4550 mg. per day to achieve the effects of the present invention.
- the compounds are preferably administered in an amount of about 4-45 mg, per day, more preferably in an amount of 12-45 mg. per day, and most preferably in a unit dose of about 4-15 mg. administered three times a day.
- the same can be administered either orally or by injection, the preferred administration route being by oral administration.
- the 5-(2- or 4-pyridyl alkyl)-amines of the invention are preferably administered in the form of a non-toxic acid addition salt thereof, and most preferably in the form of the hydrochloride.
- Example 1 Tablets are prepared by usual tabletting procedure, each tablet containing:
- the above tablet can be administered in all conditions requiring improved microcirculation. Administration of the above tablet has been found to be effective in the treatment of senility.
- Example 2 Tablets are prepared by usual tabletting procedure, each tablet containing:
- the above tablet is highly effective in improving impaired microcirculation and in thetreatment of senility.
- Example 3 Ampoules are prepared each containing 10 cc. and each cc. consisting of mg. 1-(2-pyridyl)-2-methyl amino propane hydrochloride dissolved in 0.9% sodium chloride solution. This solution can be administered parenterally to improve impaired microcirculation, and also in the treatment of senility It is believed that from the foregoing, adaptations and variations of the invention can be made without departing from the spirit or scope of the invention. Such adaptations and variations are of course intended to be comprehended within the meaning and scope of equivalents of the present invention.
- Method of improving impaired microcirculation which comprises administering to a subject requiring the same a microcirculation-improving effective amount of at least one member selected from the group consisting of BQ-pyridyl-lower alkyl)-amine, fi-(4-pyridyl-1ower alkyl)-amine and non-toxic acid addition salts thereof.
- Method of improving impaired microcirculation which comprises orally administering to a subject requiring the same a microcirculation-improving effective amount of at least one member selected from the group consisting of B (2 pyridyl lower alkyl) amine, 5-(4- pyridyl-lower alkyl)-amine and non-toxic acid addition salts thereof.
- Method of improving impaired micro-circulation which comprises administering to a subject requiring the same at least one member selected from the group consisting of ,B-(Z-pyridyl-lower alkyl)-amine, [3-(4-pyridyllower alkyl)-amine and non-toxic acid addition salts thereof in an amount of about 0.5-45 mg. per day.
- Method of improving impaired micro-circulation which comprises orally administering to a subject requiring the same at least one member selected from the group consisting of B-(Z-pyridyl-lower alkyl)-amine, p-(4-pyridyl-lower alkyl)-amine and non-toxic acid addition salts thereof in an amount of about 0.5- mg. per day.
- Method of treating senility which comprises administering to a senile patient an effective amount of at least one member selected from the group consisting of fl-(2-pyridyl-1ower alkyl)-amine, B-(4-pyridyl-lower alkyl)- amine and non-toxic acid addition salts thereof.
- Method of treating senility which comprises administering to a senile patient by oral administration an effective amount of at least one number selected from the group consisting of ,B-(Z-pyridyl-lower alkyl)-amine, B-(4-pyridyl-lower alkyl)-amine and non-toxic acid addition salts thereof.
- Method of treating senility which comprises administering to a patient at least one member selected from the group consisting of B-(Z-pyridyl-lower aIkyD-amine, p-(4-pyridyl-lower alkyl)-amine and non-toxic acid addition salts thereof in an amount of about 05-45 mg. per day.
- Method of treating senility which comprises orally administering to a patient at least one member selected from the group consisting of ,B-(Z-pyridyl-lower alkyl)- amine, fl-(4pyridyl-lower alkyl)-amine and non-toxic acid addition salts thereof in an amount of about 0.5-45 mg. per day.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pyridine Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US48623765A | 1965-09-09 | 1965-09-09 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3439096A true US3439096A (en) | 1969-04-15 |
Family
ID=23931119
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US486237A Expired - Lifetime US3439096A (en) | 1965-09-09 | 1965-09-09 | Method of improving microcirculation and treating senility with beta-(pyridyl lower alkyl)-amines |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US3439096A (enrdf_load_stackoverflow) |
| BE (1) | BE686194A (enrdf_load_stackoverflow) |
| ES (1) | ES331392A1 (enrdf_load_stackoverflow) |
| FR (1) | FR6333M (enrdf_load_stackoverflow) |
| GB (1) | GB1140540A (enrdf_load_stackoverflow) |
| IL (1) | IL26259A (enrdf_load_stackoverflow) |
| NL (1) | NL6612711A (enrdf_load_stackoverflow) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3178443A (en) * | 1963-04-01 | 1965-04-13 | Ciba Geigy Corp | N-(2-guandinoethyl)-n-(picolyl)-amines |
| US3252860A (en) * | 1963-06-05 | 1966-05-24 | Ciba Geigy Corp | Antihypertensive n-picolyl-ethylene-diamine compositions |
-
1965
- 1965-09-09 US US486237A patent/US3439096A/en not_active Expired - Lifetime
-
1966
- 1966-08-02 IL IL26259A patent/IL26259A/xx unknown
- 1966-08-03 GB GB34822/66A patent/GB1140540A/en not_active Expired
- 1966-08-19 FR FR73628A patent/FR6333M/fr not_active Expired
- 1966-08-30 BE BE686194D patent/BE686194A/xx unknown
- 1966-09-09 NL NL6612711A patent/NL6612711A/xx unknown
- 1966-09-09 ES ES0331392A patent/ES331392A1/es not_active Expired
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3178443A (en) * | 1963-04-01 | 1965-04-13 | Ciba Geigy Corp | N-(2-guandinoethyl)-n-(picolyl)-amines |
| US3252860A (en) * | 1963-06-05 | 1966-05-24 | Ciba Geigy Corp | Antihypertensive n-picolyl-ethylene-diamine compositions |
Also Published As
| Publication number | Publication date |
|---|---|
| IL26259A (en) | 1970-10-30 |
| ES331392A1 (es) | 1967-07-01 |
| BE686194A (enrdf_load_stackoverflow) | 1967-02-01 |
| GB1140540A (en) | 1969-01-22 |
| NL6612711A (enrdf_load_stackoverflow) | 1967-03-10 |
| FR6333M (enrdf_load_stackoverflow) | 1968-09-30 |
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