THIP

THIP (Gaboxadol) is a blood-brain barrier-penetrant, orally active selective GABA_A receptor agonist. THIP exhibits EC₅₀ values of 33 μM and 130 μM for α₄β₂δ and α₄β₁δ receptors, respectively. THIP activates extrasynaptic GABA_A receptors to produce tonic inhibition and inhibits GABAergic interneurons to cause disinhibition. THIP is used in research on insomnia, sleep disorders, and addictive behaviors^{[1][2][3][4][5][6]}. In Vitro:THIP (Gaboxadol) (1-30 μM) hydrobromide induces tonic GABA_A receptor-mediated currents in mouse neocortical layer 2/3 and layer 5 neurons (EC₅₀ of 44 μM for layer 2/3 neurons), decreases inhibitory activity, and enhances excitatory activity^[1].
THIP (0.34-7.0 mM; 20-120 min) hydrobromide exhibits transepithelial transport activity in Caco-2 cells^[2].
THIP (up to 1000 μM; 15-90 min) hydrobromide exhibits uptake activity in rOat1-expressing Xenopus oocytes, with a K_m of 151.2 μM and a V_max of 0.78 pmol/oocyte/min^[2].
THIP (1-10 mM) hydrobromide is a superagonist of α4β1δ, α4β2δ, and α4β3δ GABA-A receptors expressed in Xenopus oocytes, with EC₅₀ values of 33 μM and 130 μM for α4β2δ and α4β3δ, respectively^[3].
THIP (1 μM) hydrobromide decreases the frequency and amplitude of spontaneous GABA_A receptor-mediated inhibitory postsynaptic currents (sIPSCs) in dopaminergic neurons of the ventral tegmental area (VTA) in mouse midbrain slices^[5]. In Vivo:THIP (Gaboxadol) (4-6 mg/kg; i.p.; single administration; 12 h) hydrobromide induces a large-scale increase in low-frequency electroencephalogram power (SWA) during wakefulness and NREM sleep and suppresses REM sleep in wild-type mice^[4].
THIP (1-6 mg/kg; i.p.; single administration; observation from 1.5 h to 6 days) hydrobromide induces a transient decrease in spontaneous locomotor activity in Th-EGFP transgenic mice and C57BL/6J mice, and maintains long-lasting glutamate receptor plasticity in VTA dopaminergic neurons for an extended period after administration^[5].
THIP (0.3-6 mg/kg; i.p.; once every other day for a total of 8 administrations over 4 sessions; 30 min per treatment) hydrobromide exhibits activity in inducing place aversion, without producing reward effects, in the conditioned place preference model in C57BL/6J mice^[5].
THIP (0.1-3 mg/mL or 0.1-1.0 mg/kg/injection; intravenous injection; multiple administrations per day; single or 15 consecutive days) hydrobromide does not exhibit reinforcing or rewarding activity in intravenous self-administration models in adult male C57BL/6J mice and adult male olive baboons^[5].