Modulation of KCNQ potassium channel activity for treatment of psychiatric disorders and the symptoms thereof
Disclosed herein are compositions and methods for treating a psychiatric disorder or symptoms thereof in a patient. The compositions comprise a compound that modulates KCNQ (Kv7) potassium channel activity and the methods include administering an effective amount of the compound that modulates KCNQ (Kv7) potassium channel activity.
1. A method for treating a negative symptom of a psychiatric disorder in a psychiatric patient exhibiting the negative symptom, the method comprising administering an effective amount of a compound that inhibits KCNQ (Kv7) potassium channel activity to the psychiatric patient exhibiting the negative symptom, wherein the compound is linopirdine, XE991, DMP543, or a deuterated derivative or analog thereof.
2. The method of claim 1 , wherein the patient has schizophrenia.
3. The method of claim 2 , Wherein the treated negative symptom includes a symptom selected from the group consisting of flat affect, lack of motivation, anhedonia, diminished speech, social withdrawal, lack of energy, and apathy.
4. The method of claim wherein the method further treats a cognitive symptom of the psychiatric disorder in the patient.
5. The method of claim 4 , wherein the treated cognitive symptom includes a symptom selected from et the group consisting of poor executive function, loss of attention and focus, deficits in perception, difficulty in learning, working memory deficits, and problems with short- and long-term memory.
6. The method of claim 1 , further comprising administering an effective amount of a second compound for treating the psychiatric disorder.
7. The method of claim 6 , wherein the second compound for treating a psychiatric disorder is selected from the group selected from chlorpromazine, haloperidol, fluphenazine, promazine, sulpiride, clozapine, sertindole, amisulpride, zotepine, paliperidone, risperidone, aripiprazole, lamotrigine, quetiapine, perphenazine, flupenthixol, ziprasidone, olanzapine, lithium, and valproic acid.
8. The method of claim 6 , wherein the second compound is administered concurrently with the compound that inhibits KCNQ (Kv7) potassium channel activity.
9. The method of claim 6 , wherein the second compound is administered before the effective amount of a compound that inhibits KCNQ (Kv7) potassium channel activity, and optionally, the patient is refractory to treatment with the second compound.
10. The method of claim 6 , wherein the second compound is administered after the effective amount of a compound that inhibits KCNQ (Kv7) potassium channel activity.
11. The method of claim 6 , wherein the second compound treats a cognitive symptom of the psychiatric disorder in the patient or the second compound treats a positive symptom of the psychiatric disorder in the patient.
12. The method of claim 1 , wherein the compound is linopirdine or a deuterated derivative or analog thereof.
13. The method of claim 1 , wherein the compound is XE991 or a deuterated derivative or analog thereof.
14. The method of claim 1 , wherein the compound is DMP543 or a deuterated derivative or analog thereof.