Preclinical pharmacology related to anxiolysis; predictions of human dosing.

Dr. Rowlett’s current research has enormous practical as well as therapeutic applications. The lab has a long history of collaborating with pharmaceutical companies and has provided data that these companies have based their “go/no-go” decisions on for compound development. The lab is pioneering the development of primate models of anxiolysis that can predict human dosing, with plans to extend this approach to other therapeutic areas, as well as safety and toxicology. The lab’s breadth of experience also includes the preparation of documents for INDs, as well as other reports, on compound profiles, which companies have used in their discovery and development efforts.

The widespread use of anxiolytic and hypnotic drugs has created a substantial need for improved drug treatment programs. The research into the pharmacology of prescribed anxiolytic and sedative drugs has direct applications to drug development because side-effects can significantly hinder effective use of these compounds. Consequently, insights into GABA-A receptor subtype involvement in the effects of various pharmacotherapies (both marketed and in clinical development) may lead to a new generation of CNS pharmacotherapies. Dr. Rowlett’s laboratory is at the forefront of this field. 

The Rowlett lab is also investigating new clinical approaches for insomnia, developing more selective treatments that are expected to induce natural sleep patterns with less sedative side effects.

Dr. Rowlett is:

• Exploring the role of GABA-A receptors containing different subtypes of the A subunit in the anxiety-reducing, sedative, motor, and addictive effects of benzodiazepines. 
• Evaluating the extent to which certain primate models can be used to predict clinical efficacy, as well as relative potency in humans; that is, translational validity.
• Investigating the behavioral, molecular, and genetic changes associated with long-term cocaine self-administration.
• Studying the role of both positive and negative modulation of GABA-A receptors on cognition, with the ultimate goal of developing cognitive enhancing agents for a variety of disorders involving memory dysfunction. 
• Initiating new studies relating observable behavior measures of anxiolysis, rest, and sleep; and establishing telemetry systems to evaluate relationships of these quantitatively-determined behavioral effects to EEG patterns.
• Exploring alternative treatments for insomnia that display reduced side effects

Dr. Rowlett’s laboratory has been investigating the pharmacological mechanisms underlying the behavioral effects of drugs. From the program’s start, the lab has focused on developing models for CNS drug discovery efforts. Dr. Rowlett’s lab implemented a key research strategy of using non-human primates as model systems and for proof-of-concept assays in the drug discovery process.

One important area of Dr. Rowlett’s research is the lab’s long-standing focus on anxiety and anxiolysis.  Anxiety disorders are among the most frequently diagnosed disorders in psychiatric medicine. Using a multidisciplinary approach that includes collaborators in academic and industrial settings, Dr. Rowlett’s laboratory is exploring brain mechanisms, particularly GABA-A receptor mechanisms, that underlie the anti-anxiety, sedative, and addictive properties of anxiolytic medications. The lab has launched new initiatives to look into the role of GABA-A receptors in memory disturbances associated with anxiolytic drugs. The development of new drugs that retain clinical effectiveness, but lack debilitating side effects, may lead to improved treatment of anxiety disorders and related psychiatric illnesses.
 

Biological Mechanisms and Pathways

• Abuse liability •
• Central Nervous System •
• GABA •
• GABA receptor •
• Sleep
•  

Central Nervous System

• Addiction •
• Anxiety •
• Benzodiazepine •
• Cognition •
• GABA •
• Sleep
•  

Disease Mechanisms

• Addiction •
• Side effects
•  

Research Tools and Instrumentation

• Behavior model •
• Non-human primate
•  

Therapeutics

• Anxiolytic •
• Benzodiazepine •
• Muscle relaxant •
• Sedative
•