What is a CNS pharmacologic effect of ketamine and tiletamine-zolazepam?

• A. Decrease CNS response to excitatory neurotransmitters
• B. Increase GABA activity
• C. Decrease serotonin
• D. Inhibit dopamine reuptake

Answer: (A)

Ketamine and tiletamine produce their main CNS effect by blocking NMDA receptors, which are channels for the excitatory neurotransmitter glutamate. When these receptors are blocked, neuronal responses to excitatory signals are dampened, leading to dissociative anesthesia, analgesia, and altered perception. In the combination product tiletamine-zolazepam, zolazepam adds GABAergic inhibition (sedation and muscle relaxation), but the core CNS action that best fits the question is the reduction in CNS response to excitatory neurotransmitters due to NMDA receptor antagonism. The other options describe actions (increasing GABA activity, decreasing serotonin, inhibiting dopamine reuptake) that aren’t the primary CNS mechanism of these drugs.