Antipsychotic activity of 2-bromoterguride

• Applicant: Dr. Jan Brosda
• Subject Area: Cognitive, Systems and Behavioural Neurobiology ; Pharmacology
• Term: from 2014 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 260972740

Schizophrenia is a psychosis that seriously impairs the quality of life for patients. Current therapy seems to be insufficient. Therefore, great efforts are needed to develop new drugs that are effective antipsychotic medications with a diminished risk of side effects. In vitro and in vivo studies of our group suggest that 2-bromoterguride may be a second or third generation antipsychotic drug with improved efficacy in reducing negative symptoms and cognitive deficits in schizophrenia. The compound proved to be a partial agonist of low intrinsic activity at dopamine D2Short receptors and a potent antagonist at D2Long receptors. In addition, the compound showed high antagonist potencies at serotonin 5-HT2A receptors, alpha2C-adrenoceptors and low affinity for histamine H1 receptors. In vivo, 2-bromoterguride revealed antidopaminergic activity in the amphetamine-induced locomotion test without inducing catalepsy. The aim of this project is to extend the functional relevance of the receptor binding profile of 2-bromoterguride in vivo. In addition, we want to examine the potential antipsychotic efficacy of 2-bromoterguride in preclinical behavioural tests with predictive validity such as the conditioned avoidance response and the prepulse inhibition of the acoustic startle response. A further aim is to analyze the effect of 2-bromoterguride on animal models with relevance to cognitive deficits and negative symptoms. Ex vivo studies on the pharmacodynamics of 2-bromoterguride in blood and brain tissue of the rat will complete the project (effects on the tuberoinfundibular dopamine system (prolactin) and on neuronal activity (c-fos) as a molecular marker for antipsychotic activity).

• DFG Programme: Research Grants