A Preclinical Evaluation of the Discriminative And
NP5101_proof ■ 12 June 2013 ■ 1/11 Neuropharmacology xxx (2013) 1e11 Contents lists available at SciVerse ScienceDirect Neuropharmacology journal homepage: www.elsevier.com/locate/neuropharm 1 56 2 A preclinical evaluation of the discriminative and reinforcing 57 3 58 4 properties of lisdexamfetamine in comparison to D-amfetamine, 59 5 fi 60 6 methylphenidate and moda nil 61 7 62 a,* a a a b 8 Q5 David J. Heal , Niki W. Buckley , Jane Gosden , Nigel Slater , Charles P. France , 63 9 David Hackett c 64 10 65 a 11 RenaSci Ltd, BioCity Nottingham, Pennyfoot Street, Nottingham NG1 1GF, UK 66 b University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA 12 c Shire Pharmaceutical Development Ltd, Hampshire International Business Park, Chineham, Basingstoke RG24 8EP, Hampshire, UK 67 13 68 14 69 15 article info abstract 70 16 71 17 Article history: Lisdexamfetamine dimesylate, which consists of L-lysine covalently bound to D-amfetamine, is the first 72 18 Received 12 December 2012 prodrug for treating ADHD. Its metabolic conversion to yield D-amfetamine by rate-limited, enzymatic 73 19 Received in revised form hydrolysis is unusual because it is performed by peptidases associated with red blood cells. Other 74 3 April 2013 20 stimulants shown to be effective in managing ADHD include D-amfetamine, methylphenidate and 75 Accepted 13 May 2013 21 modafinil. All have the potential for misuse or recreational abuse. The discriminative and reinforcing 76 effects of these compounds were determined in rats using a 2-choice, D-amfetamine (0.5 mg/kg, i.p.)- 77 22 Keywords: cued drug-discrimination test, and by substitution for intravenous cocaine in self-administration.
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