Latest research on Lisdexamfetamine

Lisdexamfetamine (L-lysine-d-amphetamine) is a prodrug of the psychostimulant d-amphetamine coupled with the essential amino acid L-lysine. It was developed so that the amphetamine psychostimulant is released and activated more slowly as the prodrug molecule is hydrolyzed consequently cleaving off the amino acid-during the first pass through the intestines and/or the liver. Amphetamines target the trace amine-associated receptor 1 (TAAR1). Amphetamine is also believed to exert its effects by binding to the monoamine transporters (the dopamine transporter or DAT) and increasing extracellular levels of the biogenic amines dopamine, norepinephrine (noradrenaline) and serotonin.

Lisdexamfetamine dosage

Lisdexamfetamine (0.32–3.2mg/kg, i.m.) and d-amphetamine (0.032–0.32mg/kg, i.m.) were tested up to doses that produced full substitution for the Cocaine training dose. [source, 2015]
Effects of each Lisdexamfetamine dose were determined twice, whereas effects of d-amphetamine doses were determined once. [source, 2015]
The %CAR and response rates were analyzed using two-way repeated-measures analyses of variance with Lisdexamfetamine or d-amphetamine dose and time as the main fixed effects (Prism 6.0f for Mac, GraphPad). [source, 2015]
For Lisdexamfetamine studies, a Lisdexamfetamine dose (0.32–3.2mg/kg) or saline was administered i.m. between 0755 and 0805h before the start of the 0900h behavioral choice session for 7 consecutive days. [source, 2015]
Saline, Lisdexamfetamine, and d-amphetamine doses were counterbalanced across subjects. [source, 2015]
Percent Cocaine choice was then plotted as a function of the unit Cocaine dose and analyzed using a mixed-model analysis (JMP Pro 11, SAS), with Lisdexamfetamine or d-amphetamine dose and unit Cocaine dose as the fixed main effects and subject as the random effect. [source, 2015]
A post hoc Dunnett’s test was performed to compare Lisdexamfetamine or d-amphetamine effects to saline treatment effects within a unit Cocaine dose. [source, 2015]
Lisdexamfetamine produced a significant dose-dependent (F3,9 = 24.9, p = 0.0001) and time-dependent (F6,18 = 18.1, p < 0.0001) increase in cocaine-appropriate responses (interaction: F18,54 = 1.8, p = 0.0545). [source, 2015]
Doses of 1.0 and 3.2mg/kg Lisdexamfetamine produced significant cocaine-appropriate responses from 56–300min and 10min to 48h, respectively. d-amphetamine also produced a significant dose-dependent (F3,9 = 39.2, p < 0.0001) and time-dependent (F6,18 = 6.25, p = 0.0011) increase in cocaine-appropriate responses (interaction: F18,54 = 4.2, p < 0.0001). [source, 2015]
Mixed-model analyses demonstrated a significant main effect of the Lisdexamfetamine dose on Cocaine choices (F3,8 = 4.4, p = 0.0405); however, post hoc analyses using Dunnett’s test failed to detect any Lisdexamfetamine dose that significantly decreased the number of Cocaine choices earned relative to baseline. [source, 2015]