CA1090703A

CA1090703A - Thiobenzamides

Info

Publication number: CA1090703A
Application number: CA350,653A
Authority: CA
Inventors: Willy Burkard; Pierre-Charles Wyss
Original assignee: F Hoffmann La Roche AG
Current assignee: F Hoffmann La Roche AG
Priority date: 1976-03-08
Filing date: 1980-04-25
Publication date: 1980-12-02

Abstract

Abstract Pharmaceutical preparations are disclosed which contain p-chloro-N-(2-morpholinoethyl)thiobenzamide or a pharmaceutically acceptable acid addi-tion salt thereof. The active ingredient exhibits monoamineoxidase inhibiting activity.

Description

)'703 The present invention relates to pharmaceutical preparations having monoamineoxidase inhibiting activity and containing p-chloro-N-(2-morpholino-ethyl)-thiobenzamide.
In accordance with the present invention it has been found that p-chloro-N-(2-morpholinoethyl)-thiobenzamide of the formula CQ ~ C - NH - CH - CH - N ~ (I) and acid addition salts thereof possess monoamineoxidase (MAO) inhibiting activity.
The present invention is accordingly concerned with pharmaceutical preparations having MAO inhibiting activity, said preparations containing as essential active ingredient p-chloro-N-~2-morpholinoethyl)-thiobenzamide or a pharmaceutically acceptable acid addition salt thereof.
The p-chloro-N-(2-morpholinoethyl)-thiobenzamide is a known compound which is described in French Patent Specification No. 1,501,846.
As mentioned earlier, p-chloro-N-~2-morpholinoethyl)-thiobenzamide and its acid addition salts possess monoamineoxidase ~YAO) inhibiting activity.
On the basis of this activity, p-chloro-N-(2-morpholinoethyl)-thiobenzamide and its pharmaceutically acceptable acid addition salts can be used for the treatment of depressive conditions.
The MAO inhibiting activity of p-chloro-N-~2-morpholinoethyl)-thiobenzamide can be demonstrated using standard methods. Thus, p-chloro-N-~2-morpholinoethyl)-thiobenzamide was administered p.o. to rats. 1 hour after the administration, the rats were killed and the MAO inhibiting activity in the liver homogenates was measured according to the method described in Biochem.
Pharmacol. 12 ~1963) 1439-1441. The thus-ascertained activity of p-chloro-N-~, :~ .
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(2-morpholinoethyl)thiobenzamide as well as its toxicity is evident from the following ED50 value ~mol/kg, p.o. in the rat) and LD50 value ~mg/kg, p.o.
in the mouse):

Thiobenzamlde ED50 LD50 . - .
p-Chloro-N-(2-morpholinoethyl)-thiobenzamide 1250-2500 p-Chloro-N-~2-morpholinoethyl)-thiobenzamide and its pharmaceutical-ly acceptable aci~ addition salts can be used as medicaments; for example, in the form of pharmaceutical preparations which contain them in association with a pharmaceutically acceptable carrier material. This carrier material can be an organic or inorganic inert carrier material which is suitable for enteral ~e.g. oral) or parenteral administration such as, for example, water, gelatin, gum arabic, lactose, starch, magnesium stearate, talc, vegetable oils, poly-alkyleneglycols and the like. The pharmaceutical preparations can be made up in solid form (e.g. as tablets, dragees, suppositories or capsules) or in liquid form (e.g. as solutions, suspensions or emulsions). The pharmaceutical preparations may be sterilised and/or may contain adjuvants such as preserving, stabilising, wetting or emulsifying agents, salts for variation of the osmotic pressure or buffers. The pharmaceutical preparations may also contain other therapeutically valuable materials.
Convenient pharmaceutical dosage forms contain from ca 1 mg to 100 mg of p-chloro-N-(2-morpholinoethyl)-thiobenzamide or of a pharmaceutically acceptable acid addition salt thereof. Convenient oral dosage ranges lie at about 0.1 mg/kg per day to about 5 mg/kg per day. Convenient parenteral dos-age ranges lie at about 0.01 mg/kg per day to about 0.5 mg/kg per day. It will be appreciated that the aforementioned ranges can be increased or decreas-ed according to individual requirements and the directions of the attending ~'t - 2 -._ ,, .

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The following Example illustrates the present invention Example Tablets containing the following ingredients are manufactured in a manner known per se:
p-Chloro-N-(2-morpholinoethyl~-thiobenzamide 50.0 mg Lactose 95.0 mg Maize starch 100.0 mg Talc 4.5 mg Magnesium stearate 0.5 mg Weight of one tablet 250.0 mg ~, . .:: . -: . . . . . . . . .

Claims

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. A pharmaceutical preparation which contains as essential active ingredient p-chloro-N-(2-morpholinoethyl)-thiobenzamide or a pharmaceutically acceptable acid addition salt thereof, in association with a pharmaceutically acceptable carrier.