Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Patent
1996-02-23
1999-10-05
Hutzell, Paula K.
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
4353201, 435325, 536 235, 536 2431, 530350, C07H 2104, C12N 1563, C12N 1585, C07K 1400
Patent
active
059626640
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to the field of molecular biology and medicine, and more particularly to psychosis protecting (PP) nucleic acids and peptides involved in protection from psychoses and related disorders, as well as expression products, compositions thereof, and methods therefor, including detection, amplification, isolation and expression of such PP nucleic acids and PP peptides, as well as diagnostic and therapeutic methods using such PP peptides and their encoding PP nucleic acid.
2. Background of the Related Art
Psychoses, such as schizophrenia can be differentiated into two basic categories; those which are amenable to treatment, by means of conventional antipsychotic drugs, and those which are resistant to treatment, the latter usually being spoken of as "chronic" or "negative symptom" schizophrenia. Preclinical conditions of psychoses are also prevalent and could be subject to treatment if the degree of severity could be diagnosed in a standardized manner. These categories can, to some degree, be correlated with the relative balance of positive and negative symptomatology. The designation "negative (Bleulerian) symptomatology", although long known, has in recent years been used more routinely.
Treatment of psychoses and schizophrenia. Treatment of schizophrenia and other psychoses is commonly provided using the antipsychotics termed neuroleptic agents. Neuroleptic agents, regardless of their chemical structures, are pharmacologically active upon the dopamine receptor system, as dopamine antagonists. Many of these compounds, particularly the phenothiazines, also have significant activity on other neurotransmitter systems, in particular various serotonin subtypes, particularly the 5-HT-2, and on muscarinic receptors, alpha-adrenoceptors, or histamine H-1 or H-2 receptors. The clinical use of neuroleptics has provided a means for treating patients suffering from psychotic disorders, including schizophrenia. Short-term use of neuroleptics is indicated in several types of exacerbations of schizophrenia. Continuous long-term use of neuroleptics is indicated, e.g., in primary indications involving schizophrenia as well as questionable indications such as chronic characterological disorders with schizoid, "borderline," or neurotic characteristics. See, e.g., Baldessarini, Chemotherapy in Psychiatry, Revised and Enlarged Edition, Harvard University Press, Cambridge, Mass., (1985), the contents of which are entirely incorporated herein by reference.
Neuroleptics and Their Side Effects. Neuroleptics are also referred to as neuroplegics, psychoplegics, psycholeptics, antipsychotics and major tranquilizers, but are sometimes distinguished from non-neuroleptic psychotropics. Neuroleptics have also been characterized as agents that produce sedative or tranquilizing effects, and which also produce motor side effects, such as catalepsy or extrapyramidal symptomatology. Nonlimiting representative examples of neuroleptics include phenothiazine derivatives (e.g., chlorpromazine); thioxanthine derivatives (e.g., thiothixene); butyrophenone derivatives (e.g., haloperidol); dihydroindolone (e.g., molindone); dibenzoxazepine derivatives (e.g., loxapine); and "atypical" neuroleptics (e.g., sulpiride, remoxipride pimozide and clozapine). See Berstein Clinical Pharmacology Littleton, Mass.:PSG Publishing (1978); Usdin et al Clinical Pharmacology in Psychiatry New York:Elsevier North-Holland (1981); and Baldessarini, supra, (1985); which references are herein entirely incorporated by reference.
The long term use of all known anti-psychotics, including neuroleptics, has resulted in serious side effects, as set forth in Table I, such as persistent and poorly reversible motoric dysfunctions (e.g., tardive dyskinesia) in a significant number of patients. For example, classical neuroleptic agents, as exemplified by the butyrophenones and phenothiazines, can, upon long-term administration, produce severe motoric symptomatology, termed tardive dyskinesia. These motor
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Basham Daryl A.
Friedhoff Arnold J.
Miller Jeannette C.
Gucker Stephen
Hutzell Paula K.
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