Kinetic profiling of novel spirobenzo-oxazinepiperidinone derivatives as equilibrative nucleoside transporter 1 inhibitors.

Evaluation of kinetic parameters of drug-target binding, k, k, and residence time (RT), in addition to the traditional in vitro parameter of affinity is receiving increasing attention in the early stages of drug discovery. Target binding kinetics emerges as a meaningful concept for the evaluation of a ligand's duration of action and more generally drug efficacy and safety. We report the biological evaluation of a novel series of spirobenzo-oxazinepiperidinone derivatives as inhibitors of the human equilibrative nucleoside transporter 1 (hENT1, SLC29A1).

Assessment of risk factors of treatment discontinuation among patients on paliperidone palmitate and risperidone microspheres in France, Germany and Belgium.

Background: Long-acting antipsychotics (e.g. 1-monthly (PP1M) / 3-monthly (PP3M) injection forms of paliperidone palmitate) have been developed to improve treatment continuation in schizophrenia patients.

Real-World Treatment Patterns, Outcomes, Resource Utilization and Costs in Treatment-Resistant Major Depressive Disorder: PATTERN, a Retrospective Cohort Study in Belgium.

Objective: Treatment-resistant depression (TRD), a subgroup of major depressive disorder (MDD) that does not adequately respond to treatment, has a substantial impact on the quality of life of patients and is associated with higher medical and mental health care costs. This study aimed to report real-world treatment patterns, outcomes, resource utilization, and costs in the management of TRD by psychiatrists in Belgium.

Methods: We conducted a retrospective, non-interventional cohort study of patients ≥ 18 years, with diagnosed MDD who are treatment-resistant, defined as not responding to two different antidepressant treatments in the current moderate to severe major depressive episode (MDE).

Potent and selective pharmacodynamic synergy between the metabotropic glutamate receptor subtype 2-positive allosteric modulator JNJ-46356479 and levetiracetam in the mouse 6-Hz (44-mA) model.

Objective: We previously demonstrated that positive allosteric modulators (PAMs) of metabotropic glutamate subtype 2 (mGlu ) receptors have potential synergistic interactions with the antiseizure drug levetiracetam (LEV). The present study utilizes isobolographic analysis to evaluate the combined administration of JNJ-46356479, a selective and potent mGlu PAM, with LEV as well as sodium valproate (VPA) and lamotrigine (LTG).

Methods: The anticonvulsant efficacy of JNJ-46356479 was evaluated in the 6-Hz model of psychomotor seizures in mice.

Efficacy of mGlu -positive allosteric modulators alone and in combination with levetiracetam in the mouse 6 Hz model of psychomotor seizures.

Objective: The metabotropic glutamate receptor subtype 2 (mGlu ) possesses both orthosteric and allosteric modulatory sites, are expressed in the frontal cortex and limbic structures, and can affect excitatory synaptic transmission. Therefore, mGlu is a potential therapeutic target in the treatment of epilepsy. The present study seeks to evaluate the anticonvulsant potential of mGlu -acting compounds.