WO1990006114A1

WO1990006114A1 - Use of dihydroergotamine for the treatment of increased intracranial pressure

Info

Publication number: WO1990006114A1
Application number: PCT/SE1989/000689
Authority: WO
Inventors: Per-Olof GRÄNDE
Original assignee: Graende Per Olof
Priority date: 1988-11-28
Filing date: 1989-11-27
Publication date: 1990-06-14
Also published as: SE463445B; SE8804285D0; SE8804285L

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 Orstanorm^v^^/ (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

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.