The invention provides a method of sustained delivery of a lactam, imide, amide, sulfonamide, carbamate or urea containing parent drug by administering to a patient an effective amount of a prodrug compound of the invention wherein upon administration to the patient, release of the parent drug from the prodrug is sustained release. Prodrug compounds suitable for use in the methods of the invention are labile conjugates of parent drugs that are derivatized through carbonyl linked prodrug moieties. The prodrug compounds of the invention can be used to treat any condition for which the lactam, imide, amide, sulfonamide, carbamate or urea containing parent drug is useful as a treatment.

Prodrugs of nh-acidic compounds

Lactam compounds of Formula I and their use for the treatment of neurological and psychiatric disorders including schizophrenia, bipolar disorder, anxiety disorder and insomnia is disclosed.

Heterocyclic Compounds for the Treatment of Neurological and Psychological Disorders

Prodrugs of nh-acidic compounds: ester, carbonate, carbamate and phosphonate derivatives

Compositions and methods for the treatment of depression and psychoses in humans are disclosed More particularly, the invention is directed to formulations containing antipsychotic and/or antidepressant medications and also containing an NMDAR antagonist The present Invention Is also directed to methods tor the treatment of humans suffering from depression and other psychoses, including, schizophrenia, by administration of the inventive compositions in antidepressant and/or antipsychotic effective amounts

Composition and method for treatment of depression and psychosis in humans

The invention provides a method of sustained delivery of a tertiary amine-containing parent drug comprising administering to a patient an effective amount of a prodrug compound of the invention wherein upon administration to the patient, release of the parent drug from the prodrug is sustained release. Prodrug compounds suitable for use in the methods of the invention are labile quaternary ammonium salts of tertiary amine-containing parent drugs (or tertiary imine-containing parent drugs) that are derivatized through aldehyde-linked prodrug moieties that reduce the solubility of the prodrug compound at a reference pH as compared to the parent drug. The physical, chemical and solubility properties of these derivatives can be further modulated by the choice of counterion X". In one embodiment, the present invention provides a prodrug compound of Formula I: where R1-R5 are defined in the written description of the invention. The prodrug compounds of the invention can be used to treat any condition for which the tertiary amine-containing parent drug or tertiary imine-containing parent drug is useful as a treatment.

Quaternary ammonium salt prodrugs

Combinations of 5-HT2A inverse agonists or antagonists such as pimavanserin with antipsychotics such as risperidone are shown to induce a rapid onset of antipsychotic action and increase the number of responders when compared to therapy with the antipsychotic alone. These effects can be achieved at a low dose of the antipsychotic, thereby reducing the incidence of side effects. The combinations are also effective at decreases the incidence of weight gain and increased glucose or prolactin levels caused by the antipsychotic.

Combinations of 5-ht2a inverse agonists and antagonists with antipsychotics

Combination of pimavanserin and risperidone for the treatment of psychosis

L'invention concerne des combinaisons d'agonistes ou antagonistes inverses de 5-HT2A tels que la pimavanserine avec des antipsychotiques tels que la risperidone pour induire un depart rapide d'une action antipsychotique et augmenter le nombre de repondeurs en comparaison a une therapie avec seulement l'antipsychotique. Ces effets peuvent etre atteints a une faible dose de l'antipsychotique, reduisant ainsi l'incidence des effets secondaires. Les combinaisons sont egalement efficaces pour diminuer l'incidence de la prise de poids et des taux accrus de glucose ou de prolactine induits par l'antipsychotique.

David Furlano

Papers

Combinations of 5-ht2a inverse agonists and antagonists with antipsychotics

Combination of pimavanserin and risperidone for the treatment of psychosis

Combinaisons d'agonistes ou antagonistes inverses de 5-ht2a avec antipsychotiques