Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1996-10-09
1998-01-27
Jarvis, William R.A.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514392, 514424, A61K 3152, A61K 31415, A61K 3140
Patent
active
057122822
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/JP95/00736, filed Apr. 14, 1995.
TECHNICAL FIELD
This invention relates to a new pharmaceutical composition for therapeutically treating tardive dyskinesia, which comprises a compound having an enzyme-inhibitory activity against enzymatic functions of phosphodiesterases as an active ingredient, and this invention also relates to uses of said composition.
BACKGROUND ART
Tardive dyskinesia is a disease which is accompanied with chronic and involuntary movements appearing in the face, head or trunk of the patients which are incurred in association with long-term administration of various drugs, mainly such antipsychotic drugs, especially a curative drug for schizophrenia, that act as an antagonist to dopamine D.sub.2 receptors of the dopamine neuron system in the corpus striatum of the brain. The time of occurrence of said involuntary movements is found at a time of from several months to several years lapsed from the starting of the administration of the above antipsychotic drugs. In some case, said disease can occur even when the dosage of said antipsychotic drug had been reduced or when the administration of the drug had been withdrawn. This disease can often continue for a long time even when the withdrawal of the administration of the antipsychotic drugs had been made. Some portions of the involuntary movements may often be irreversible, namely be refractory.
For example, haloperidol is a compound of butyrophenone-type and is such a representative drug for treating schizophrenia, which acts as the antagonist against the dopamine D.sub.2 receptors present in the dopamine neuron system in the corpus striatum of the brain. Haloperiodol has been used extensively in the clinics for nearly 40 years. However, it is well known that a long-term administration of haloperidol brings about induction of tardive dyskinesia as an adverse reaction.
The above-mentioned involuntarily occurring abnormal movements of tradive dyskinesia appear mainly in the muscles around the mouth and appear also in the facial muscles, particularly the muscles of cheeks, tongue and jaws and are characterized by mumble-like movements, but these involuntary movements can sometime appear also in the head, trunk and limbs. Tardive dyskinesia is neurologically classified as a hyper-activity of extra-pyramidal system in central motor pathway which is connecting to the spinal motor neuron, and tardive dyskinesia is thought to be attributable to a defficiency of the inhibitory mechanism in corpus striatum of the brain. Problems to be solved in clinical practice for this disease are such that the abnormal movements of tardive dyskinesia would continue even after the withdrawal of the medication with the antipsychotic drugs and eventually become chronic and ultimately become refractory (see Inada T, K. Ohnishi, M. Kamisada, G. Matsuda, O. Tajima, Y. Yanagisawa, K. Hashiguchi, S. Shima, Y. Oh-e, Y. Masuda, T Chiba, K. Kamijima, R. W. Rockhold and G. Yagi, "A prospective study of tardive dyskinesia in Japan", Psychiat. Clin. Neurosci., 240, pp. 250-254 (1991)). However, any curative drugs which are sufficiently effective to tardive dyskinesia have not been discovered yet so far. In case tardive dyskinesia has occurred, there is no alternative but to withdraw the administration of the antipsychotic drugs to the patients or to reduce the dosage of these drugs. These methods of withdrawing the administration of the antipsychotic drugs or of reducing the dosage of these drugs can bring about an aggravation or recurrence of the initial psychosis and hence cannot necessarily provide a really effective measure for treating the patients. Accordingly, it is now demanded for a long time to provide a curative drug which is effective and useful to therapeutically treat tardive dyskinesia.
A hypothesis has been presented to suppose that, in case of the occurrence of tardive dyskinesia which is induced by a long-term administration of the antipsychotic drugs, the dopamine D.sub.2 receptors present in the dopamine neuron system
REFERENCES:
Budavari, Ed., The Merck Index, Eleventh Edition pp. 1312-1313, entry No. 8235 1989.
Hashimoto Kenji
Inada Toshiya
Iyo Masaomi
Kitao Yoshie
Maeda Yohko
Iyo Masaomi
Jarvis William R.A.
Meiji Seika Kaisha Ltd.
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