Heteromeric nicotinic inhibition by isoflurane does not mediate MAC or loss of righting reflex.

Background: Neuronal nicotinic acetylcholine receptors (nAChRs) have been implicated in the mechanism of action of isoflurane as they are inhibited at subanesthetic concentrations. Despite clear evidence for nicotinic inhibition at relevant isoflurane concentrations, it is unclear what behavioral result ensues, if any.

Methods: The authors have modeled two behaviors common to all general anesthetics, immobility and hypnosis, as minimum alveolar concentration that prevents movement in response to a supramaximal stimulus (MAC) and loss of righting reflex (LORR).

Isoflurane hyperalgesia is modulated by nicotinic inhibition.

Background: The inhaled anesthetic isoflurane inhibits neuronal nicotinic acetylcholine receptors (nAChRs) at concentrations lower than those used for anesthesia. Isoflurane produces biphasic nociceptive responses, with both hyperalgesia and analgesia within this concentration range. Because nicotinic agonists act as analgesics, the authors hypothesized that inhibition of nicotinic transmission by isoflurane causes hyperalgesia.

Sensitivity of the alpha7 nicotinic acetylcholine receptor to isoflurane may depend on receptor inactivation.

Unlabelled: In previous studies, we demonstrated that nicotinic acetylcholine receptors (nAChRs) composed of the alpha7 subunit are unaffected by the co-application of isoflurane with agonists at concentrations up to 640 microM (two times the minimum alveolar anesthetic concentration). Modulation of alpha7-nAChR activity by isoflurane might have important behavioral ramifications because these receptors are expressed diffusely in the central and peripheral nervous systems and play pre- and postsynaptic roles in synaptic transmission. Here we have demonstrated that under some potentially physiologically relevant circumstances, the activation of alpha7 nAChRs may be inhibited by clinically relevant concentrations of isoflurane.

Droperidol inhibits GABA(A) and neuronal nicotinic receptor activation.

Background: Droperidol is used in neuroleptanesthesia and as an antiemetic. Although its antiemetic effect is thought to be caused by dopaminergic inhibition, the mechanism of droperidol's anesthetic action is unknown. Because gamma-aminobutyric acid type A (GABAA) and neuronal nicotinic acetylcholine receptors (nAChRs) have been implicated as putative targets of other general anesthetic drugs, the authors tested the ability of droperidol to modulate these receptors.