Why are Mechanisms of Anesthesia So Difficult to Elucidate?

Difficult to link anesthetic effects observed in vitro to intact animals
No structure–activity relationships are apparent
Wide variety of structurally unrelated compounds (steroids to xenon) are capable of producing anesthesia
Suggests multiple molecular mechanisms can produce anesthesia
Anesthetics work at very high concentrations (contrasts with drugs, hormones, and neurotransmitters that bind at specific receptors)
If anesthetics act at receptors, must bind with low affinity and for short periods (difficult to observe and characterize)