Elucidation of the molecular mechanisms by which general anesthetics act is an important goal in clinical medicine and neuropharmacology. It is necessary for the development of safer and more specific anesthetic agents, and for the safe use of available agents while minimizing their inherent toxicities.
Work from our laboratory and from others indicates that general anesthetics act primarily on synaptic transmission. At clinically relevant concentrations, most general anesthetics depress excitatory synaptic transmission while some facilitate inhibitory synaptic transmission—including the intravenous agents propofol, etomidate, and barbiturates.
There is good evidence for both presynaptic and postsynaptic mechanisms for these effects, including presynaptic reductions in excitatory neurotransmitter release, inhibition of postsynaptic responses to excitatory neurotransmitters, and facilitation of postsynaptic and extrasynaptic responses to inhibitory neurotransmitters. However, the precise molecular mechanisms involved in these effects are unknown.
Volatile anesthetics decrease presynaptic Ca²⁺ entry, and processes that determine nerve terminal excitability and...
An inherent problem in comparing differences in presynaptic pharmacology between glutamatergic and GABAergic neurons is the diversity in GABAergic interneuron subtypes. Interneurons modulate...
Ca²⁺ influx through presynaptic voltage-gated Ca²⁺ channels (Caᵥ) is required for neurotransmitter release. Volatile anesthetic effects on synaptic transmission and neurotransmitter release...
Advances in structural biology have begun to reveal drug binding sites on Naᵥ, but sites of anesthetic interactions with mammalian Naᵥ are unavailable due to a lack of detailed structural...