New Research Areas

Clearly the tremendous advances, however controversial, in the understanding of targets for anesthetics have enhanced the possibility of discovering novel agents. A key question is what precisely can be improved in new agents over currently used agents. It seems highly likely that this question will have to be initially addressed at the molecular level in vitro using electrophysiological approaches to identify NCEs that can be evaluated in behavioral and telemeterized rodent models.

6.15.7.1 Anesthetic-Specific Benzodiazepines (BZs)

Like advances in subunit-selective GABAA receptor ligands for use in the treatment of anxiety,52 it is to be anticipated that, with additional knowledge of the precise regions/subunits of the GABAA receptor involved in anesthetic induction, improved parenteral anesthetics may be feasible. One approach may be the development of improved neurosteroids that are more soluble than alphaxalone (see 6.04 Anxiety).

6.15.7.2 Melatonin

2-Bromomelatonin (Figure 4) is comparable to propofol in its rapid induction and short duration of activity in rodent models of anesthetic activity while being 6-10 times less active.53 Unlike propofol, the antinocifensive activity of 2-bromomelatonin persisted after the anesthetic effect, as measured by the fact that the righting reflex had ceased. 2-Bromomelatonin analogs may represent another novel approach to parenteral anesthesia.54

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