Methylphenidate is not clastogenic in cultured human lymphocytes and in the mouse bone-marrow micronucleus test.
Methylphenidate (MPH) is one of the most frequently prescribed drugs for the treatment of attention deficit hyperactivity disorder (ADHD). A report on cytogenetic effects observed in peripheral lymphocytes from children treated for 3 months with MPH raised questions about the genetic toxicity of this compound. A critical review of this data concluded that the cytogenetic effects in treated children remain unexplained. A literature review showed that MPH was found negative in most genetox studies performed, but no in vitro chromosome aberration data in human lymphocytes have been published. Therefore, we conducted a chromosomal aberration study in cultured human peripheral lymphocytes. The results of this investigation showed that d,l-methylphenidate (MPH, Ritalin) in concentrations up to 10 mM did neither induce structural nor numerical chromosome abnormalities. An oral mouse bone-marrow micronucleus test in B6C3F(1) mice, with doses up to 250 mg/kg bw, was negative too. The data of these studies confirm the absence of clastogenic activity of MPH in non-clinical studies.
Suter
Willi
W
Safety Assessment and Profiling, Exploratory Development, Novartis Pharma AG, MUT-2881.2.35, CH4002 Basel, Switzerland. willi.suter@novartis.com
Martus
Hans-Joerg
HJ
Elhajouji
Azeddine
A
D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D000697:Central Nervous System Stimulants / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology*; D008774:Methylphenidate / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D051379:Mice; D008815:Mice, Inbred Strains; D015162:Micronucleus Tests / Q000379:methods*; D008956:Models, Chemical; D009153:Mutagens / Q000494:pharmacology*; D013997:Time Factors
D000697:Central Nervous System Stimulants; D009153:Mutagens; D008774:Methylphenidate