WO1990006114A1 - Use of dihydroergotamine for the treatment of increased intracranial pressure - Google Patents
Use of dihydroergotamine for the treatment of increased intracranial pressure Download PDFInfo
- Publication number
- WO1990006114A1 WO1990006114A1 PCT/SE1989/000689 SE8900689W WO9006114A1 WO 1990006114 A1 WO1990006114 A1 WO 1990006114A1 SE 8900689 W SE8900689 W SE 8900689W WO 9006114 A1 WO9006114 A1 WO 9006114A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- dihydroergotamine
- intracranial pressure
- treatment
- pressure
- solution
- Prior art date
Links
- 229960004704 dihydroergotamine Drugs 0.000 title claims abstract description 17
- HESHRHUZIWVEAJ-JGRZULCMSA-N dihydroergotamine Chemical compound C([C@H]1C(=O)N2CCC[C@H]2[C@]2(O)O[C@@](C(N21)=O)(C)NC(=O)[C@H]1CN([C@H]2[C@@H](C3=CC=CC4=NC=C([C]34)C2)C1)C)C1=CC=CC=C1 HESHRHUZIWVEAJ-JGRZULCMSA-N 0.000 title claims abstract description 17
- 206010022773 Intracranial pressure increased Diseases 0.000 title abstract description 5
- 238000007917 intracranial administration Methods 0.000 claims abstract description 10
- 150000003839 salts Chemical class 0.000 claims abstract description 4
- 210000003625 skull Anatomy 0.000 claims abstract description 4
- 230000001154 acute effect Effects 0.000 claims abstract description 3
- 238000001802 infusion Methods 0.000 claims description 5
- 208000027418 Wounds and injury Diseases 0.000 abstract description 3
- 230000006378 damage Effects 0.000 abstract description 3
- 208000014674 injury Diseases 0.000 abstract description 3
- 230000007423 decrease Effects 0.000 description 5
- 210000004556 brain Anatomy 0.000 description 4
- 230000000694 effects Effects 0.000 description 3
- 210000003205 muscle Anatomy 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000002889 sympathetic effect Effects 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 208000001089 Multiple system atrophy Diseases 0.000 description 1
- 206010031127 Orthostatic hypotension Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000001949 anaesthesia Methods 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 229960004943 ergotamine Drugs 0.000 description 1
- OFKDAAIKGIBASY-VFGNJEKYSA-N ergotamine Chemical compound C([C@H]1C(=O)N2CCC[C@H]2[C@]2(O)O[C@@](C(N21)=O)(C)NC(=O)[C@H]1CN([C@H]2C(C3=CC=CC4=NC=C([C]34)C2)=C1)C)C1=CC=CC=C1 OFKDAAIKGIBASY-VFGNJEKYSA-N 0.000 description 1
- XCGSFFUVFURLIX-UHFFFAOYSA-N ergotaminine Natural products C1=C(C=2C=CC=C3NC=C(C=23)C2)C2N(C)CC1C(=O)NC(C(N12)=O)(C)OC1(O)C1CCCN1C(=O)C2CC1=CC=CC=C1 XCGSFFUVFURLIX-UHFFFAOYSA-N 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 210000005036 nerve Anatomy 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/48—Ergoline derivatives, e.g. lysergic acid, ergotamine
Definitions
- the present invention relates to a new use of dihydroergotamine.
- Dihydroergotamine (ergot alkabid) is presently used in medical care for treating orthostatic hypo- tension, as a blood pressure increasing agent at cer ⁇ tain regional anaesthesia and for reducing headache of migraine type.
- Dihydroergotamine (DHE) is conside ⁇ red to exercise its effect by relatively selective constriction of venous capacitance vessels.
- DHE is an allowed pharmaceutical prepara ⁇ tion and is sold in Sweden under the trade name Orstanorm v ⁇ / (Sandoz) .
- dihydro ⁇ ergotamine significantly decreases intracranial pres- sure which has increased by e " .g. violence against the skull.
- the present invention relates to a new use of dihydroergotamine, namely for the treatment of increased intracranial pressure in order to reduce said pressure e.g. after an acute skull injury.
- the administration of dihydroergotamine for trea ⁇ ting humans is preferably carried out by intravenous or sucutan infusion and at intravenous infusion either intermittent or continuously.
- Subsequent fig. 1 shown the effect of the treat- • ment with dihydroergotamine on four patients represen ⁇ ted on panels A, B, C and D.
- the patient in panel D was given two doses of dihydroergotamine of 0,2 mg i.v. in each dose according to the arrow in the figure.
- the remaining three patients were given only one dose in accordance with arrows in each figure.
- the intracranial pressure is reduced significantly in all four patients about 3-5 minutes after the admini ⁇ stration of dihydroergotamine.
- the low pressure is maintained for
- suitable doses may be kept within the range of 1 - 25 ug/kg/dosage occaision at -intermittent dosage, which is repeated 25 times every twenty-four hours. At continuous infusion, the dose may vary between 0,5 and 30 ug/kg/h.
- the treatment may be carried out using dihydroergotamine as well as a pharmaceutically acceptable salt or solution thereof and suitable doses may be given with regard to known factors such as the type and degree of injury and the condition and .weight of the person.
- the treatment may be carried out on humans as well as animals when de-. sired.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to use of dihydroergotamine or a pharmaceutical salt or solution thereof for the treatment of increased intracranial pressure in order to reduce said intracranial pressure e.g. after an acute skull injury in humans.
Description
Use of dihydroergotamine for the treatment of increased intracranial pressure.
The present invention relates to a new use of dihydroergotamine.
Dihydroergotamine (ergot alkabid) is presently used in medical care for treating orthostatic hypo- tension, as a blood pressure increasing agent at cer¬ tain regional anaesthesia and for reducing headache of migraine type. Dihydroergotamine (DHE) is conside¬ red to exercise its effect by relatively selective constriction of venous capacitance vessels. For these indications, DHE is an allowed pharmaceutical prepara¬ tion and is sold in Sweden under the trade name Orstanormv^/ (Sandoz) .
A data search with the key words "intracranial pressure" and "increased intracranial pressure" in combination with DHE has not lead to any result, i.e. dihydroergotamine is not. known in connection with "intracranial pressure".
It has surprisingly been noticed that dihydro¬ ergotamine significantly decreases intracranial pres- sure which has increased by e".g. violence against the skull.
Therefore, the present invention relates to a new use of dihydroergotamine, namely for the treatment of increased intracranial pressure in order to reduce said pressure e.g. after an acute skull injury.
. The invention- will be further described below with reference to the accompanying drawings, wherein fig. 1 illustrates the effect of the treatment of four patients and fig. 2 shows the result of experiments on skeleton musculature.
The administration of dihydroergotamine for trea¬ ting humans is preferably carried out by intravenous or sucutan infusion and at intravenous infusion either intermittent or continuously. Subsequent fig. 1 shown the effect of the treat- •
ment with dihydroergotamine on four patients represen¬ ted on panels A, B, C and D. The patient in panel D was given two doses of dihydroergotamine of 0,2 mg i.v. in each dose according to the arrow in the figure. The remaining three patients were given only one dose in accordance with arrows in each figure. As is apparent, the intracranial pressure is reduced significantly in all four patients about 3-5 minutes after the admini¬ stration of dihydroergotamine. As is further apparent from the panels, the low pressure is maintained for
45-75 minutes, whereafter it slowly rises but stabili¬ zes at a level below the original pressure.
For methodological reasons and the complex ana¬ tomy of the brain it is today not possible to study possible mechanisms behind the registered decrease of intracranial pressure directly on the vessels of " the brain. Therefore, studies have instead been made on skeleton musculature, more specifically on the calf- muscle of a cat. The sympathetic nerves of this calf muscle have been cut in order to imitate the vessel control of the brain which has so sympathetic control. The result of these studies (five experiments) is shown in fig. 2. In this figure, panel A illustrates that precapillary resistance (R_) increases more than postcapillary resistance (R ), meaning that the capil¬ lary pressure decreases as indicated in panel B. Thus, this decrease reduction of the capillary pressure induces a transport of liquid from the tissue into the blood vessel designated absorption rate, as is illustrated in panel C.
These results offer a conceivable explanation to the registered intracranial pressure reduction, pro¬ vided that the result from the skeleton muscle can be applied onto the brain circulation. Thus, it is apparent from the results that in the first place, a quick pressure reduction is obtained possibly because of a constriction of the blood rich venous capacitance vessels and secondly, a slow but
continuous decrease of the tissue volume possibly be¬ cause of the reduced capillary pressure, which of course also means a reduced intracranial pressure. This latter mechanism may in the long run pro- bably be the most important for curing this type of patients.
During treatment suitable doses may be kept within the range of 1 - 25 ug/kg/dosage occaision at -intermittent dosage, which is repeated 25 times every twenty-four hours. At continuous infusion, the dose may vary between 0,5 and 30 ug/kg/h.
Finally, it can be mentioned that the treatment may be carried out using dihydroergotamine as well as a pharmaceutically acceptable salt or solution thereof and suitable doses may be given with regard to known factors such as the type and degree of injury and the condition and .weight of the person. The treatment may be carried out on humans as well as animals when de-. sired.
Claims
1. Use of dihydroergotamine or a pharmaceutical salt or solution thereof for the treatment of increa¬ sed intracranial pressure in order to reduce said intracranial pressure e.g. after an acute skull in- jury in humans.
2. Use according to claim 1, whereby dihydroergo¬ tamine or a pharmaceutical salt or solution thereof is administered in doses within the range of 1-25 ug/kg/ /dosage occasion at intermittent dosage of up to 25 times every twenty-four hours.
3. Use according to claim 1, whereby dihydroergo¬ tamine or a pharmaceutical -salt or solution thereof is administered by continous infusion at a rate of infusion varying between 0,5 and 30 ug/kg/h, prefera- bly 2-8 ^g/kg/h.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE8804285-8 | 1988-11-28 | ||
| SE8804285A SE463445B (en) | 1988-11-28 | 1988-11-28 | APPLICATION OF DIHYDROERGOTAMINE FOR PREPARING A MEDICINE FOR TREATMENT OF HIGHLY INTRACRANIAL PRESSURE |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1990006114A1 true WO1990006114A1 (en) | 1990-06-14 |
Family
ID=20374079
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/SE1989/000689 WO1990006114A1 (en) | 1988-11-28 | 1989-11-27 | Use of dihydroergotamine for the treatment of increased intracranial pressure |
Country Status (2)
| Country | Link |
|---|---|
| SE (1) | SE463445B (en) |
| WO (1) | WO1990006114A1 (en) |
-
1988
- 1988-11-28 SE SE8804285A patent/SE463445B/en not_active IP Right Cessation
-
1989
- 1989-11-27 WO PCT/SE1989/000689 patent/WO1990006114A1/en unknown
Non-Patent Citations (2)
| Title |
|---|
| KIRK-OTHERM, ENCYCLOPEDIA OF CHEMICAL TECHNOLOGY, third edition, Volume 1, pages 909-912. * |
| PATHOPHYSIOLOGY AND PHARMACOTHERAPY OF CEREBROVASCULAR DISORDERS, Satellite Symposuim of the XXVIII International Congress of Physiological Sciences, 1980, pages 431-435, J. LEPAGNOL et al.: "Histological studies and their relation to metabolic and biochemical changes after drug treatment with regard to intercranial * |
Also Published As
| Publication number | Publication date |
|---|---|
| SE8804285L (en) | 1990-05-29 |
| SE463445B (en) | 1990-11-26 |
| SE8804285D0 (en) | 1988-11-28 |
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