Ansofaxine hydrochloride (LY03005) is a serotonin-norepinephrine-dopamine reuptake inhibitor (IC50s: 723, 763 and 491 nM, respectively).

Dopamine:491 nM, Norepinephrine:763 nM, 5-HT:723 nM

Acute administration was performed by providing rodents with oral solutions (0.06 mmol/kg p.o.), oral suspensions (0.06 mmol/kg p.o.) and intravenous solutions (0.04 mmol/kg i.v.) of Ansofaxine and desvenlafaxine. Oral suspensions (0.06 mmol/kg/day) of the two drugs were also administered for a 14-day chronic period. Ansofaxine rapidly penetrated the rat striatum, converted into desvenlafaxine and exhibited larger total exposure compared with the administration of desvenlafaxine. Acute and chronic administration of oral suspension of Ansofaxine increased the 5-HT, DA and NE levels more than the relative administration of desvenlafaxine [1]. The maximum tolerated dose (MTD) was 500mg/kg and the lethal dose was 1000mg/kg in SD rats after a single administration of Ansofaxine. In 13-week repeated-dose oral toxicity, the no-observed-adverse-effect level (NOAEL) of Ansofaxine was greater than 300mg/kg for rats [2].

The dosages of LPM570065 and desvenlafaxine used with different administration routes referred to previous studies and was determined by preliminary experiments. Oral solutions of LPM570065 and desvenlafaxine for intragastric administration (0.06 mmol/kg p.o.) were prepared by dissolving the compounds in 10% glucose. Oral suspensions of LPM570065 and desvenlafaxine for intragastric administration (0.06 mmol/kg p.o.) were prepared by suspending the compounds in 0.5% carboxymethylcellulose sodium. Intravenous solutions of LPM570065 and desvenlafaxine for intravenous administration (0.04 mmol/kg i.v.) were prepared by dissolving the compounds in 10% glucose. WAY-100635 was dissolved in 0.9% saline and was administered subcutaneously (0.3 mg/kg s.c.). Raclopride was dissolved in 0.9% saline and was administered subcutaneously (0.5 mg/kg s.c.). Different vehicles were used for administration using different administration routes [1].