Comparative Electroencephalographic Profile of a New Anesthetic and Anticonvulsant That Is Selective for the GABA A R Slow Receptor Subtype.

Background: Anesthetics like propofol increase electroencephalography (EEG) power in delta frequencies (0.1-4 Hz), with a decrease of power in bandwidths >30 Hz. Propofol is nonselective for gamma amino butyric acid type A receptor subtypes (GABA A R) as it enhances all 3 GABA A R subtypes (slow, fast, and tonic).

Modulation of α1β3γ2 GABA receptors expressed in oocytes using a propofol photoswitch tethered to the transmembrane helix.

Tethered photoswitches are molecules with two photo-dependent isomeric forms, each with different actions on their biological targets. They include reactive chemical groups capable of covalently binding to their target. Our aim was to develop a β-subunit-tethered propofol photoswitch (MAP20), as a tool to better study the mechanism of anesthesia through the GABA α1β3γ2 receptor.

A newly developed anesthetic based on a unique chemical core.

Intravenous anesthetic agents are associated with cardiovascular instability and poorly tolerated in patients with cardiovascular disease, trauma, or acute systemic illness. We hypothesized that a new class of intravenous (IV) anesthetic molecules that is highly selective for the slow type of γ-aminobutyric acid type A receptor (GABAR) could have potent anesthetic efficacy with limited cardiovascular effects. Through in silico screening using our GABAR model, we identified a class of lead compounds that are -arylpyrrole derivatives.

An In Vitro Model for Identifying Cardiac Side Effects of Anesthetics.

The understanding of anesthetic side effects on the heart has been hindered by the lack of sophisticated clinical models. Using micropatterned human-induced pluripotent stem cell-derived cardiomyocytes, we obtained cardiac muscle depressant profiles for propofol, etomidate, and our newly identified anesthetic compound KSEB01-S2. Propofol was the strongest depressant among the 3 compounds tested, exhibiting the largest decrease in contraction velocity, depression rate, and beating frequency.