Learn More
In brachiation, an animal uses alternating bimanual support to move beneath an overhead support. Past brachiation models have been based on the oscillations of a simple pendulum over half of a full cycle of oscillation. These models have been unsatisfying because the natural behavior of gibbons and siamangs appears to be far less restricted than so(More)
Phosphodiesterase 10A (PDE10A) is a novel target for the treatment of schizophrenia that may address multiple symptomatic domains associated with this disorder. PDE10A is highly expressed in the brain and functions to metabolically inactivate the important second messengers cAMP and cGMP. Here we describe effects of a potent and orally bioavailable PDE10A(More)
The cognitive deficits associated with schizophrenia are recognized as a core component of the disorder, yet there remain no available therapeutics to treat these symptoms of the disease. As a result, there is a need for establishing predictive preclinical models to identify the therapeutic potential of novel compounds. In the present study, rhesus monkeys(More)
The current standards of care for Alzheimer’s disease, acetylcholinesterase inhibitors, have limited efficacy due to a host of mechanism-related side effects arising from indiscriminate activation of muscarinic and nicotinic receptors. The M1 muscarinic receptor is predominantly expressed in the brain in regions involved in cognition, and therefore(More)
Reduced NMDA receptor functioning is hypothesized to underlie the cognitive and negative symptoms associated with schizophrenia. However, because direct activation of the NMDA receptor is accompanied by neurotoxicity, mechanisms that activate the glycine co-agonist site on the NMDA receptor could carry greater therapeutic potential. In the current study,(More)
Current treatments for insomnia, such as zolpidem (Ambien) and eszopiclone (Lunesta), are γ-aminobutyric acid type A (GABAA)-positive allosteric modulators that carry a number of side effects including the potential to disrupt cognition. In an effort to develop better tolerated medicines, we have identified dual orexin 1 and 2 receptor antagonists (DORAs),(More)
The standards of care for Alzheimer’s disease, acetylcholinesterase inhibitors such as donepezil (Aricept®), are dose-limited due to adverse side-effects. These adverse events lead to significant patient non-compliance, constraining the dose and magnitude of efficacy that can be achieved. Non-selective muscarinic receptor orthosteric agonists such as(More)
Improved treatment of Alzheimer disease (AD) is a significant unmet medical need that is becoming even more critical given the rise in the number of patients and the substantial economic burden. The current standards of care, acetylcholinesterase inhibitors (AChEIs), are hindered by gastrointestinal side effects owing to their nonselective activation of(More)
  • 1