CTDP-32476

CTDP-32476 is a dopamine transporter (DAT) inhibitor with a K_i value of 12 nM for human DAT, and exhibits moderate affinity for norepinephrine transporter (NET). CTDP-32476 blocks DAT to increase extracellular dopamine levels, induces motor enhancement and brain stimulation reward effects in rats, inhibits self-administration behavior and cue-induced relapse behavior, and shows no reinforcing activity with low addiction potential. CTDP-32476 can be used in studies related to addiction to tropane alkaloid psychostimulants^[1]. In Vitro:CTDP-32476 (10 nM-100 μM; 60 min) potently binds to human DAT expressed in HEK293 cells, with a K_i value of 12 nM^[1].
CTDP-32476 (10 pM-100 μM; 60 min) is a potent competitive inhibitor of human DAT expressed in HEK293 cells, which inhibits the binding of [³H]-cocaine to DAT, with a K_i value of 0.12 nM at the high-affinity site and 123 nM at the low-affinity site^[1].
In Vivo:CTDP-32476 (0.5-1.0 mg/kg; intravenous injection; administered for 3 hours daily for 10 consecutive days) does not exhibit cocaine hydrochloride-like rewarding properties in naive rats^[1].
CTDP-32476 (0.5 mg/kg; intravenous injection; administered daily for 3 hours for 7 consecutive days) fails to maintain the schedule-controlled intravenous self-administration behavior in rats trained to self-administer a Schedule II psychostimulant^[1].
The rewarding efficacy of CTDP-32476 (0.25-1.0 mg/kg; intravenous injection; administered daily for 3 consecutive days) is significantly lower than that of psychostimulants^[1].
CTDP-32476 (3-20 mg/kg; i.p.; single administration) dose-dependently suppresses schedule-controlled self-administration behavior under a fixed ratio 2 reinforcement schedule in rats with a history of stimulant exposure^[1].
Pretreatment with CTDP-32476 (3-20 mg/kg; intraperitoneal injection; single administration) reduces the rewarding efficacy of psychostimulants, with a significant effect observed at the dose of 20 mg/kg^[1].
Pretreatment with CTDP-32476 (10-20 mg/kg; intraperitoneal injection; single administration) dose-dependently reduces psychostimulant self-administration behavior and total intake in rats with a history of psychostimulant exposure within a certain dose range^[1].
Chronic daily administration of CTDP-32476 (10-20 mg/kg; i.p.; once daily for 7 consecutive days) during extinction training significantly reduces cue-induced relapse of controlled stimulant-seeking behavior in rats with a history of controlled stimulant exposure^[1].
Systemic administration of CTDP-32476 (10-20 mg/kg; i.p.; single dose) slowly induces a persistent increase in dopamine (DA) levels in the nucleus accumbens, and both systemic administration and local perfusion of CTDP-32476 (30 μM; local perfusion in the nucleus accumbens; single dose) attenuate the cocaine-induced elevation of extracellular DA levels in the nucleus accumbens^[1].
Systemic administration of CTDP-32476 (3-10 mg/kg; i.p.; single dose) induces slow-onset, long-lasting, dose-dependent enhancement of spontaneous activity in rats, an effect that differs from the rapid-onset action of cocaine^[1].
Systemic administration of CTDP-32476 (3-10 mg/kg; i.p.; single dose) produces a slow-onset, long-lasting, and dose-dependent enhancement of brain stimulation reward in rats, which differs from the rapid-onset effect of cocaine^[1].