Adaptive, dose-finding phase 2 trial evaluating the safety and efficacy of ABT-089 in mild to moderate Alzheimer disease.

ABT-089, an α4β2 neuronal nicotinic receptor partial agonist, was evaluated for efficacy and safety in mild to moderate Alzheimer disease patients receiving stable doses of acetylcholinesterase inhibitors. This phase 2 double-blind, placebo-controlled, proof-of-concept, and dose-finding study adaptively randomized patients to receive ABT-089 (5, 10, 15, 20, 30, or 35 mg once daily) or placebo for 12 weeks. The primary efficacy endpoint was the Alzheimer's Disease Assessment Scale, cognition subscale (ADAS-Cog) total score.

A randomized pilot study of the efficacy and safety of ABT-089, a novel α4β2 neuronal nicotinic receptor agonist, in adults with attention-deficit/hyperactivity disorder.

Objective: ABT-089, an α4β2 neuronal nicotinic receptor partial agonist (generic name pozanicline), has demonstrated efficacy in adults with attention-deficit/hyperactivity disorder (ADHD) at doses of 40 mg once daily and 40 mg twice daily. The purpose of this exploratory pilot study was to obtain initial safety, tolerability, and efficacy data for an ABT-089 80-mg once-daily regimen to inform a decision of whether to include an 80-mg once-daily dose regimen in subsequent, definitive (phase 3) efficacy studies.

Method: This phase 2, randomized, double-blind, parallel-group, placebo-controlled pilot study was conducted at 12 sites from March to August 2008.

A double-blind, randomized, placebo-controlled study of the dopamine D₃ receptor antagonist ABT-925 in patients with acute schizophrenia.

There is substantial preclinical and clinical evidence to suggest a potential role for the dopamine D₃ receptor in the treatment of schizophrenia. ABT-925 is a selective dopamine D₃ receptor antagonist with an approximately 100-fold higher in vitro affinity for dopamine D₃ versus D₂ receptors. This double-blind, randomized, placebo-controlled, escalating-dose, parallel-group study assessed the efficacy and safety of ABT-925 in the treatment of patients with acute exacerbation of schizophrenia.

Safety and efficacy of ABT-089 in pediatric attention-deficit/hyperactivity disorder: results from two randomized placebo-controlled clinical trials.

Objective: To assess the safety and efficacy of ABT-089, a novel α(4)β(2) neuronal nicotinic receptor partial agonist, vs. placebo in children with attention-deficit/hyperactivity disorder (ADHD).

Method: Two multicenter, randomized, double-blind, placebo-controlled, parallel-group studies of children 6 through 12 years of age were conducted.

Divalproex sodium extended-release for the prophylaxis of migraine headache in adolescents: results of a stand-alone, long-term open-label safety study.

Objective: The objective of this long-term open-label study in adolescents was to assess the safety and tolerability of divalproex sodium extended-release in the prophylaxis of migraine headaches.

Background: Two formulations of divalproex sodium have demonstrated efficacy in the prevention of migraine headaches in adults. However, no medications are currently approved for this indication in adolescents, and long-term safety data on agents for migraine prevention are lacking for this younger population.

Safety and tolerability of divalproex sodium extended-release in the prophylaxis of migraine headaches: results of an open-label extension trial in adolescents.

Objective: To evaluate the long-term safety and tolerability of divalproex sodium extended-release in the prophylaxis of migraine headaches in adolescents.

Background: Divalproex sodium has been approved for migraine prophylaxis in adults. A previous double-blind, placebo-controlled study of the efficacy and safety of divalproex sodium extended-release for prevention of migraine in adolescents was followed by the present long-term extension trial, which was designed to collect additional safety and tolerability data.

Divalproex extended-release in adolescent migraine prophylaxis: results of a randomized, double-blind, placebo-controlled study.

Objective: To evaluate the efficacy, tolerability, and safety of 3 different doses of divalproex sodium extended-release vs placebo in the prophylaxis of migraine headaches in adolescents.

Background: Divalproex sodium has been approved for migraine prophylaxis in adults, and previous uncontrolled data suggest divalproex sodium may be effective in preventing migraine in children and adolescents with acceptable tolerability.

Methods: This was a 12-week, phase 3, randomized, placebo-controlled, double-blind, parallel-group, multicenter study in approximately 300 adolescents aged 12 to 17 years with migraine headaches.

Delta-9-tetrahydrocannabinol effects in schizophrenia: implications for cognition, psychosis, and addiction.

Background: Recent advances in the neurobiology of cannabinoids have renewed interest in the association between cannabis and psychotic disorders.

Methods: In a 3-day, double-blind, randomized, placebo-controlled study, the behavioral, cognitive, motor, and endocrine effects of 0 mg, 2.5 mg, and 5 mg intravenous Delta-9-tetrahydrocannabinol (Delta-9-THC) were characterized in 13 stable, antipsychotic-treated schizophrenia patients.

Extracellular metabolites in the cortex and hippocampus of epileptic patients.

Interictal brain energy metabolism and glutamate-glutamine cycling are impaired in epilepsy and may contribute to seizure generation. We used the zero-flow microdialysis method to measure the extracellular levels of glutamate, glutamine, and the major energy substrates glucose and lactate in the epileptogenic and the nonepileptogenic cortex and hippocampus of 38 awake epileptic patients during the interictal period. Depth electrodes attached to microdialysis probes were used to identify the epileptogenic and the nonepileptogenic sites.

Striking differences in glucose and lactate levels between brain extracellular fluid and plasma in conscious human subjects: effects of hyperglycemia and hypoglycemia.

Brain levels of glucose and lactate in the extracellular fluid (ECF), which reflects the environment to which neurons are exposed, have never been studied in humans under conditions of varying glycemia. The authors used intracerebral microdialysis in conscious human subjects undergoing electrophysiologic evaluation for medically intractable epilepsy and measured ECF levels of glucose and lactate under basal conditions and during a hyperglycemia-hypoglycemia clamp study. Only measurements from nonepileptogenic areas were included.