Riluzole and D-amphetamine interactions in humans.
In preclinical studies, medications which decrease glutamate release have been shown to block some of the effects of psychostimulants. One such medication is riluzole, marketed for the treatment of Amyotrophic Lateral Sclerosis (ALS). The goal of this study was to determine riluzole's effects on acute physiological and subjective responses to d-amphetamine in healthy volunteers. Seven male and 5 female subjects participated in an outpatient double-blind, placebo-controlled, crossover study. Across 4 sessions, subjects were randomly assigned to a sequence of 4 oral treatments: placebo, 20 mg D-amphetamine alone, 100 mg riluzole alone, or d-amphetamine plus riluzole. Outcome measures included heart rate, blood pressure, plasma cortisol, performance on the Sustained Attention to Response Test (SART), and subjective measures. d-amphetamine increased heart rate, blood pressure and plasma cortisol levels while inducing psychostimulant-type subjective effects. On the SART, d-amphetamine enhanced the speed of correct responses but also significantly increased the number of errors of commission. Riluzole at 100 mg did not block, the typical subjective and physiological responses to 20 mg D-amphetamine. Riluzole alone induced amphetamine-like subjective responses. On the SART test, riluzole increased the number errors of commission, but unlike d-amphetamine, did not speed reaction time. The mechanism accounting for these findings is unclear, but may involve processes other than decreased glutamate release by riluzole. The effects of glutamate medications on psychostimulant responses need to be further examined.
Sofuoglu
Mehmet
M
Yale University, School of Medicine, Department of Psychiatry and VA Connecticut Healthcare System, 950 Campbell Ave., Bldg. 36/116A4, West Haven, CT 06516, United States. Mehmet.Sofuoglu@yale.edu
Waters
Andrew J
AJ
Mooney
Marc
M
Kosten
Thomas
T
D000328:Adult; D019540:Area Under Curve; D001794:Blood Pressure / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects; D018592:Cross-Over Studies; D003913:Dextroamphetamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004347:Drug Interactions / Q000502:physiology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D009483:Neuropsychological Tests; D017063:Outcome Assessment, Health Care / Q000379:methods; D011930:Reaction Time / Q000187:drug effects; D019782:Riluzole / Q000494:pharmacology*; D013997:Time Factors
D000697:Central Nervous System Stimulants; D019782:Riluzole; D003913:Dextroamphetamine; D006854:Hydrocortisone
Brain Res. 1994 Jan 7;633(1-2):312-6
7907936
Annu Rev Pharmacol Toxicol. 1993;33:639-77
8494354
Biol Psychiatry. 1996 Jan 1;39(1):26-32
8719123
Psychiatry Res. 1996 Aug 30;64(1):1-10
8888359
Neurology. 1996 Dec;47(6 Suppl 4):S233-41
8959995
Neuropsychologia. 1997 Jun;35(6):747-58
9204482
Crit Rev Neurobiol. 1998;12(1-2):37-67
9444481
Neurosci Lett. 1998 Feb 13;242(2):114-6
9533407
J Clin Psychopharmacol. 2004 Dec;24(6):665-9
15538132
Drug Alcohol Depend. 2005 Feb 14;77(2):151-9
15664716
Biol Psychiatry. 2005 Feb 15;57(4):430-2
15705360
J Comp Neurol. 2005 Mar 28;484(1):43-56
15717303
J Neurosci. 2005 Aug 10;25(32):7342-51
16093384
J Subst Abuse Treat. 2005 Sep;29(2):85-93
16135337
Biol Psychiatry. 2005 Sep 1;58(5):424-8
15993857
Alcohol Clin Exp Res. 2006 Sep;30(9):1451-65
16930207
Psychopharmacology (Berl). 2006 Oct;188(2):162-70
16915378
Neuropsychopharmacology. 2007 Apr;32(4):793-802
16936714
Lancet. 2003 May 31;361(9372):1878-9
12788585
Psychopharmacology (Berl). 2000 Aug;151(2-3):226-33
10972469
Prog Neurobiol. 2001 Feb;63(3):241-320
11115727
Neuropsychobiology. 2001;43(2):91-5
11174052
Psychopharmacology (Berl). 2000 Dec;153(1):85-92
11255931
Neuropsychologia. 2002;40(1):1-6
11595257
J Subst Abuse Treat. 2001 Dec;21(4):193-8
11777668
Arch Gen Psychiatry. 2002 May;59(5):409-16
11982444
Dev Neuropsychol. 2002;21(1):43-71
12058835
J Pharmacol Exp Ther. 2002 Sep;302(3):1265-71
12183688
Nature. 2003 Jan 2;421(6918):70-5
12511956
J Neuropsychiatry Clin Neurosci. 2003 Winter;15(1):98-104
12556579
Mol Psychiatry. 2003 Apr;8(4):373-82
12740594
Neuropsychobiology. 2003;48(1):27-30
12886037
Drug Alcohol Depend. 2003 Aug 20;71(2):143-52
12927652
J Neurosci. 2003 Oct 22;23(29):9500-7
14573529
Ann N Y Acad Sci. 2003 Nov;1003:169-75
14684444
Neuron. 2004 Sep 30;44(1):161-79
15450168
Am J Psychiatry. 2004 Nov;161(11):2132
15514421
Ann N Y Acad Sci. 1992 Jun 28;654:171-91
1632582
Psychopharmacology (Berl). 1993;111(1):1-16
7870923