Ace Therapeutics' conventional microdialysis technology can be used in multiple aspects of the antipsychotic drug development process, including studies of drug absorption, distribution, metabolism, efficacy, and toxicity, helping to accelerate the drug development process and select the optimal drug dose and delivery regimen.

Introduction of Conventional Microdialysis in Antipsychotic Drug Development

Various improvements have made in vivo microdialysis an extremely effective method for studying highly dynamic neurotransmitter responses in stress physiology and behavior. Microdialysis can collect virtually any substance from the brain of freely moving animals with limited tissue trauma. It allows the measurement of local neurotransmitter release in conjunction with ongoing behavioral changes (e.g., locomotion). In addition, microdialysis can be used to measure free corticosterone levels in the brain, thus allowing simultaneous monitoring of hypothalamic-pituitary-adrenocortical (HPA) axis activity and neurotransmission.

Fig. 1 Principles of intracerebral microdialysis in awake, freely moving mice. (Gardier AM. 2013)

Conventional Microdialysis Services

Ace Therapeutics analyzes a variety of neurotransmitters in the extracellular space of the rodent brain by microdialysis. We help you understand the dynamic changes in the concentration of molecules involved in intercellular communication and metabolism in awake, freely moving animals by combining microdialysis with sensitive bioanalytical techniques to provide the most comprehensive information. We can measure the local release of neurotransmitters, neurometabolites, and other small endogenous substances in free-moving or anesthetized rodents. We have developed methods to measure acetylcholine, choline, histamine, amino acids and monoamines.

Our Process

The principle of microdialysis is based on the balance between the release of neurotransmitters (e.g., monoamines) and the reuptake of selective transporters (e.g., the 5-hydroxytryptamine transporter for 5-hydroxytryptamine). This technique can be used as a complement to electrophysiology to reflect presynaptic monoamine release and intrasynaptic events.

Typically, we use male 3- to 4-month-old wild-type (WT) or mutant mice (weighing 25-30 g) for microdialysis experiments. During this experiment, we typically collect samples every 10 or 20 minutes at a flow rate of 0.5 to 1.5μl/min, depending on the experimental protocol and the brain region under study. These samples contained molecules such as serotonin and its major metabolites, NE, DA and its metabolites. We then quantified these molecules by using high-performance LC coupled with an amperometric detector.

Our Microdialysis Technology in Antipsychotics Discovery

• Drug uptake and distribution studies: We can monitor the uptake and distribution of antipsychotic drugs in brain tissue in animal models with our microdialysis technology to help you understand the pharmacokinetics of the drug in the organism.
• Studies of drug metabolism: We can monitor the metabolism of antipsychotic drugs in brain tissue by microdialysis techniques to help you understand drug metabolic pathways and metabolites.
• Drug potency and toxicity studies: We can help you evaluate the potency and toxicity of anti-psychotic drugs by using microdialysis technology to select the optimal drug dose and dosing regimen.
• Study of pharmacodynamic parameters during drug development: We can monitor the effects of antipsychotic drugs directly in vitro or in animals through microdialysis technology, including the drug's duration of action, dose-response relationship, etc.

Ace Therapeutics is committed to helping you better understand the molecular interactions between monoaminergic systems, pre- and postsynaptic partners, neuronal circuits, and related regions of the brain, and we aim to help you overcome the limitations of current treatments and identify new therapeutic targets. If you are interested in this service, please make an inquiry to learn how we can support you in your project.

Reference

1. Gardier AM. Antidepressant activity: contribution of brain microdialysis in knock-out mice to the understanding of BDNF/5-HT transporter/5-HT autoreceptor interactions. Front Pharmacol. 2013, 4:98.