IE55181B1 - Treatment of minimal brain dysfunction(mbd) - Google Patents

Description

-2- -2- &51S 1 This invention is directed to the treatment of Minimal Brain Dysfunction in humans.

The term Minimal Brain Dysfunction is defined herein as any condition characterized by inattention and 5 impulsivity. The condition may be with or without hyperactivity and usually has an onset before age 7 and a duration greater than six months. For further detail concerning the symptoms or diagnosis of minimal brain dysfunction also known as ATTENTION DEFICIT Disorder, see 10 the Quick Reference to the Diagnostic Criteria from DSM-111, (c) The American Psychiatric Association, 1980, pp. 26 to 29 (314.01 and 314.80). Also, see Minimal Brain Dysfunction is Children, (6) John Wiley and Sons Inc., 1971 for additional information.

According to the invention there is provided use of m-chloro-ir-t-butylaminopropiophenone of the formula -3- -3- 5518 1 or a pharmaceutically acceptable acid addition salt thereof in the preparation of a pharmaceutical composition for the treatment of minimal brain dysfunction as hereinbefore defined in a human being.

In U.S. Patents Nos. 3,819,706 and 3,885,046, the compound of formula I (named m-chloro-α-t-butylaminopropiophenone) and salts thereof were disclosed as being antidepressants.

The most common pharmacological treatment of MBD (this includes the childhood disorder of hyperactivity or 10 hyperkinesis) is administration of stimulant drugs, such as methamphetamine, pemoline or methylphenidate. In the U.S.A., a few million children are treated annually for this disorder. While these drugs are effective in many cases they often cause a reduction in the growth of 15 children and have an abuse liability. The drugs also tend to exert sympathomimetic effects of increase in heart rate and blood pressure.

The compound or salts of formula I offers the advantages of exhibiting fewer of the aforementioned effects than 20 occur with methamphetamine, pemoline and methylphenidate. In particular, the compound or salts of formula I does not reduce body growth, does not elevate blood pressure or pulse rate, and has a lower likelihood of producing drug dependence or drug abuse. -4- -4- 55181 The compound of formula (I) (the active ingredient) or the pharmaceutically acceptable acid addition salt thereof is preferably administered in unit dosage form to the human being treated.

A pharmaceutical composition containing a compound of formula (I), or a pharmaceutically acceptable salt thereof, may be presented in discrete units such as tablets, capsules, ampules or suppositories, each containing an effective amount of the compound or salt for 10 treatment of minimal brain dysfunction.

As an example, for the treatment of humans having minimal brain dysfunction the preferred unit dosage of a compound of formula (I) or an acid addition salt thereof (as the base) for oral administration, or administration as a 15 suppository, is about 15 milligrams to 500 milligrams, preferably 15 milligrams to 300 milligrams, and the most preferred unit dosage is 25 milligrams to 75 milligrams per day, (t.i.d.). three times a day for a 20 to 40 kg child. Therapeutic (effective) dosage in humans is 20 preferably 1 to 10 mg\kg (orally) per day in order to treat a patient. Treatment is given on a continuous basis to a person who had already been identified as having minimal brain dysfunction. All the above doses are given in terms of the weight of a compound of formula (I) in -5- -5- 5 5181 the form of its base, but as will be appreciated from the foregoing information, it may be administered in the form of a pharmaceutically acceptable acid addition salt thereof. Parenteral administration may be used and in 5 this case the parenteral dose would be about 1/2 the oral dosage.

A compound of formula (I) or pharmaceutically acceptable salts thereof may be presented as an oral unit preparation (for example as a cachet, tablet or capsule) containing 10 one or more pharmaceutically acceptable carriers which may take the form of solid diluents such as lactose, cornstarch, micronized silica gel as well as other excipients known in the art.

It should be understood that in addition to the 15 aforementioned ingredients, the pharmaceutical composition of this invention may include one or more of additional ingredients e.g., pharmaceutically acceptable carriers such as diluents, buffers, flavouring agents, binders, surface active agents, thickeners, lubricants, 20 preservatives, and the like. The formulations may be prepared by admixture of the ingredients, and, if necessary, shaping the resulting mass, and filling into suitable containers. -6- -6- 55181 The compound used in this invention is preferably presented for use as a pharmaceutically acceptable acid addition salt. Examples of some of the pharmaceutically acceptable salts which can be utilized are salts of the 5 following acids: hydrochloric, sulfuric, phosphoric and toluenesulphonic.

Reference should be had to U.S. Patents 3,819,706 and 3,885,046, which are incorporated herein by reference hereto for a description of the preparation of the 10 compound of formula (I), acid addition salts thereof, tablets, capsules, parenteral solutions and suppositories incorporating same.

EXAMPLE 1 The hydrochloride salt of formula X is administered as a 15 tablet to a child who has been identified by a clinician as having the symptoms associated with minimal brain dysfunction. A child is orally administered a daily dose of 6 mg/kg (calculated as base) in three equally divided doses 6 hours between doses.

The child is treated continuously for several years and -7- -7- 55181 fchen taken off the drug periodically to determine if the underlying pathology is resolved. If not treatment is reinstituted, 180 mg is administered to 30 kg child daily.

EXAMPLE II The procedure of Example 1 is followed however the hydrochloride salt at the same dosage is orally administered as an orange flavored aqueous solution, 1 teaspoon three times daily (60 mg base per spoonful).

Claims (10)

1. Use of m-chloro-W-£-butylaminopropiophenone or a pharmaceutically acceptable acid addition salt thereof in the preparation of a pharmaceutical composition for the 5 treatment of minimal brain dysfunction as hereinbefore defined in a human being.

2. Use according to claim 1 of a pharmaceutically acceptable acid addition salt.

3. Use according to claim 1 of the hydrochloride 10 addition salt.

4. Use of a compound defined in any of claims 1 to 3 for the preparation of a composition as defined in claim 1, suitable for oral administration.

5. Use of a compound defined in any of claims 1 15 to 3 for the preparation of a composition as defined in claim 1, suitable for parenteral administration.

6. Use of a compound defined in any of claims 1 to 3 for the preparation of a composition as defined in claim 1, suitable for rectal administration. -9- 5 51 8 ί

7. Use of a compound defined in any of claims 1 to 3 for the preparation of a composition as defined in claim 1 in unit dosage form.

8. Use of a compound defined in any of claims 1 5 to 3 for the preparation of a composition as defined in claim 1 in the form of an orally ingestible tablet.

9. Use of a compound defined in any of claims 1 to 3 for the preparation of a composition as defined in claim 1 in the form of an orally ingestible capsule.

10. Use of m-chloro-oi-t- butylaminopropiophenone or a pharmaceutically acceptable acid addition salt thereof substantially as hereinbefore described with reference to the Examples. DATED THIS 13TH DAY OF MAY 1982 CRUICKSHANK AND COMPANY Agents for the Applicants 1 Holies Street Dublin 2.