Table 3.

Effects of CAR and DDCAR in rodent models of psychosis, cognition, and EPS activity

Test	Species	CAR ED50a (mg/kg, p.o.)	DDCAR ED50 (mg/kg, p.o.)
Spontaneous locomotor activity	Rat	0.18	1.8
Amphetamine (0.5 mg/kg, s.c.)-induced hyperactivity	Rat	0.12	0.66
MK-801 (0.2 mg/kg, i.p.)-induced hyperactivity	Mouse	0.049	0.18
Phencyclidine (2.5 mg/kg, s.c.)-induced hyperactivity	Rat	0.09	0.23
Apomorphine (1.5 mg/kg, s.c.)-induced climbing	Mouse	0.27	0.84
Conditioned avoidance response	Rat	0.84	2.2
Scopolamine (3 mg/kg, i.p.)-induced learning impairment in the water labyrinth	Rat	0.02–0.2b	0.5–2
Catalepsy	Rat	>85	>100

Notes: CAR or DDCAR were administered p.o. in a volume of 5 mL/kg in rats and 10 mL/kg in mice. The test compounds were suspended in 2–6% Tween 80, depending on the dose and requirement for sufficient suspension homogeneity. Solutions required for doses in the lower milligram per kilogram range were usually diluted from a stock solution/suspension. Dose–response curves were generated with 5–6 dose groups and each dose group consisted of 10 (rats) and 12 (mice) animals. ^aCAR values are republished from Neurochemistry International, 59(6), Gyertyan I, Kiss B, Saghy K, et al, Cariprazine (RGH-188), a potent D3/D2 dopamine receptor partial agonist, binds to dopamine D3 receptors in vivo and shows antipsychotic-like and procognitive effects in rodents, 930, Copyright (2011), with permission from Elsevier.14 ^bEffective dose range.

Abbreviations: CAR, cariprazine; DDCAR, didesmethyl-cariprazine; EPS, extrapyramidal symptoms; i.p., intraperitoneal; p.o., per os; s.c., subcutaneous.