Date of Award
The Evaluation of AZ66, A Highly Selective Sigma-1 and Sigma-2 Antagonist, for Anticonvulsive Effects in C57Bl/6 Mice (Under the direction of Lisa Wilson and Dr. Christopher McCurdy) Sigma receptors have become a popular subject for research the past few decades, but there is still much mystery behind these receptors and how they work. Researchers have found that sigma receptor antagonists can attenuate cocaine induced convulsions, however, limited research has been conducted on the effects of these antagonists on convulsions that mimic the types of seizures associated with epilepsy. Therefore, the aim of the current study was to evaluate AZ66 (20 mg/kg i.p.), a highly selective sigma 1 & 2 receptor antagonist, against pentylenetetrazole (PTZ) (80 mg/kg s.c.) induced convulsions. The first aim of the study was to determine the optimal dose and dosing method for the administration of PTZ in our laboratories. Both subcutaneous (s.c.) and intraperitoneal (i.p.) injections were separately investigated at 50-80 mg/kg and 30-60 mg/kg doses respectively. The second aim was to find the minimum dose of AZ66 that was effective at reducing or attenuating PTZ induced convulsions. The AZ66 dose was administered one hour before the PTZ dose administration. Seizure latency and frequency were recorded. The subcutaneous 80 mg/kg dose of PTZ was chosen due to its fast response time and clear distinction between seizures. AZ66 decreased seizure latency and increased seizure frequency and resulted in death when given at the 30mg/kg dose. Further studies on the role of the sigma receptors in epilepsy are needed.
Stone, Jamie, "The Evaluation of AZ66, A Highly Selective Sigma-1 and Sigma-2 Receptor Antagonist, For Its Anti-Convulsive Effects in C57BL/6 Mice" (2017). Honors Theses. 425.