as GABAA receptors can influence cell proliferation. Ligands A number of ligands have been found to bind to various sites on the GABAA receptor complex and modulate it besides GABA itself. A ligand can possess one or more properties of the following types. Unfortunately the literature often does not distinguish these types properly. Types Orthosteric agonists and antagonists: bind to the main receptor site (the site where GABA normally binds, also referred to as the "active" or "orthosteric" site). Agonists activate the receptor, resulting in increased Cl− conductance. Antagonists, though they have no effect on their own, compete with GABA for binding and thereby inhibit its action, resulting in decreased Cl− conductance. First order allosteric modulators: bind to allosteric sites on the receptor complex and affect it either in a positive (PAM), negative (NAM) or neutral/silent (SAM) manner, causing increased or decreased efficiency of the main site and therefore an indirect increase or decrease in Cl− conductance. SAMs do not affect the conductance, but occupy the binding site. Second order modulators: bind to an allosteric site on the receptor complex and modulate the effect of first order modulators. Open channel blockers: prolong ligand-receptor occupancy, activation kinetics and Cl ion flux in a subunit configuration-dependent and sensitization-state dependent manner. Non-competitive channel blockers: bind to or near the central pore of the receptor complex and directly block Cl− conductance through the ion channel. Examples Orthosteric agonists: GABA, gaboxadol, isoguvacine, muscimol, progabide, beta-alanine, taurine, piperidine-4-sulfonic acid (partial agonist). Orthosteric antagonists: bicuculline, gabazine. Positive allosteric modulators: barbiturates, benzodiazepines, certain carbamates (ex. carisoprodol, meprobamate, lorbamate), Honokiol, Magnolol, Baicalin, Baicelin, thienodiazepines, alcohol (ethanol), etomidate, glutethimide, kavalactones, meprobamate, quinazolinones (ex. methaqualone, etaqualone, diproqualone), neuroactive steroids, niacin/niacinamide, nonbenzodiazepines (ex. zolpidem, eszopiclone), propofol, stiripentol, theanine, valerenic acid, volatile/inhaled anesthetics, lanthanum, and riluzole. Negative allosteric modulators: flumazenil, Ro15-4513, sarmazenil, Pregnenolone sulfate, amentoflavone, and zinc. Inverse allosteric agonists: beta-carbolines (ex. Harmine, Harmaline, Tetrahydroharmine). Second-order modulators: (−)‐epigallocatechin‐3‐gallate. Non-competitive channel blockers: cicutoxin, oenanthotoxin, pentylenetetrazol, picrotoxin, thujone, and lindane. Effects Ligands which contribute to receptor activation typically have anxiolytic, anticonvulsant, amnesic, sedative, hypnotic, euphoriant, and muscle relaxant properties. Some such as muscimol and the z-drugs may also be hallucinogenic. Ligands which decrease receptor activation usually have opposite effects, including anxiogenesis and convulsion. Some of the subtype-selective negative allosteric modulators such as α5IA are being investigated for their nootropic effects, as well as treatments for the unwanted side effects of other GABAergic drugs. Novel drugs