| Juvenile toxicity assessment of d,l-methylphenidate in rats. | |
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MedLine Citation:
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PMID: 18189274 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: The oral administration of d,l-methylphenidate (MPH) was designed to encompass the major part of postnatal development in the rat and to evaluate potential chronic effects. METHODS: Wistar Hannover rats were cross-fostered on postpartum day 0 (day of birth) and were administered MPH at doses of 5, 50, and 100 mg/kg/day (mpkd) on postpartum days 7 to 70. Clinical signs, body weight, food consumption, developmental, behavioral, clinical/anatomic pathology, toxicokinetic, and fertility evaluations were conducted. RESULTS: MPH-related effects on clinical signs, body weight, and behavior tests were noted. Increased locomotor activity and cage biting/chewing occurred at > or =5 mpkd (females) and > or =50 mpkd (males) and were absent after dosing ceased. Body weight parameters were decreased at > or =50 mpkd and were comparable to controls at 5 weeks' recovery. Open field motor activity tests conducted 2 weeks after dosing ceased revealed decreased peripheral beam breaks at > or =50 mpkd. Passive avoidance tests conducted 3 weeks after dosing ceased indicated decreased females reaching learning criterion at 100 mpkd. This is considered of nominal significance as there were no effects in the water maze test or retention in passive avoidance test. After multiple doses, females exhibited higher exposures than males and exposures were reduced in all groups in comparison to those after a single dose. CONCLUSIONS: These results suggest that MPH can produce enduring behavioral effects in rats. The no-toxicologic-effect-level was 5 mpkd, associated with AUC((0-24 h)) racemate values in males and females, respectively, of 101 and 153 ng.h/mL after chronic dosing. |
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Authors:
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David A Beckman; Marilynn Schneider; Maureen Youreneff; Francis L S Tse |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Birth defects research. Part B, Developmental and reproductive toxicology Volume: 83 ISSN: 1542-9741 ISO Abbreviation: Birth Defects Res. B Dev. Reprod. Toxicol. Publication Date: 2008 Feb |
Date Detail:
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Created Date: 2008-02-28 Completed Date: 2008-03-13 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101155115 Medline TA: Birth Defects Res B Dev Reprod Toxicol Country: United States |
Other Details:
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Languages: eng Pagination: 48-67 Citation Subset: IM |
Copyright Information:
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(c) 2008 Wiley-Liss, Inc. |
Affiliation:
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Safety Profiling & Assessment, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey 07936, USA. david.beckman@novartis.com |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Animals, Newborn Avoidance Learning / drug effects Behavior, Animal / drug effects* Body Weight / drug effects Central Nervous System Stimulants / toxicity* Dose-Response Relationship, Drug Female Fertility / drug effects Male Maze Learning / drug effects Methylphenidate / toxicity* Motor Activity / drug effects No-Observed-Adverse-Effect Level Rats Rats, Wistar Stereoisomerism |
| Chemical | |
Reg. No./Substance:
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0/Central Nervous System Stimulants; 113-45-1/Methylphenidate |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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