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46012924.der.pdf
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46012924
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Hydrogen maleate and mecamylamine
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77086-21-6, 60-40-2
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605204, 600090
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Milburn, G. (2003) Dizocilpine and Mecamylamine: Positive Control Water Maze Study in Rats: Final Report. Project Number: WR0442. Unpublished study prepared by Central Toxicology Lab (Syngenta). 111 p.
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2003.0
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Dizocilpine and Mecamylamine: In a positive control water maze study in rats (59 days old) using dizocilpine and mecamylamine, (MRID 46012924), groups of twenty Alpk:APfSD (Wistar-derived) rats/sex were administered vehicle control (saline), 0.3 mg/kg of dizocilpine or 10 mg/kg of mecamylamine in one intraperitoneal dose, and tested in the water-filled Y maze 30 minutes later (learning phase), and 4 days later (memory phase).
In control animals, there was clear evidence of learning and memory. At a dizocilpine dose of 0.3 mg/kg, 7 males and 14 females had reduced stability; six of these females were unsuitable for testing on the day of treatment and had to be tested in the learning phase the next day. On day 1 for both sexes, mean swim times for straight channel and all trials during the learning phase were greater than the controls and swim times did not decrease with subsequent trials compared to trial 1. When expressed as the percentage of animals with successful trials at a specified cut-off, males were significantly less than controls at 3 sec and females were significantly less at 5 sec; the percentage of successful trials as a multiple of the individual straight channel swim time was similar between the treated and control groups. On day 4 for both sexes, swim times for trial 1 were greater than the controls, but all subsequent trials and straight channel were faster than the controls. During the memory phase, swim times decreased with subsequent trials compared with trial 1 in females, and decreased in Trial 6 in males. Females had a significantly greater percentage of successful trials at 5 sec.
Twenty males and 19 females treated with mecamylamine showed half closed eyes and dilated pupils. On day 1 for males and females straight channel and all trial swim times were similar to the controls; times for subsequent trials decreased compared to trial 1. On day 4, some variability was observed but in general swim times were similar to the control group for all trials except for trials 3 and 6 in males, where there was an increase in swim time compared to controls.
This study is classified Acceptable/Non-guideline. Central Toxicology Laboratory has demonstrated proficiency in this study for detecting changes in Y water maze learning and memory in postnatal (59 days old) Alpk:APfSD (Wistar-derived) rats due to dizocilpine treatment (results for mecamylamine were erratic as described in the literature) for the time period around 2001 (in life period of study). This positive control study does not satisfy any guideline requirement.
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Other
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NA [870.6300, Developmental neurotoxicity study]
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Intraperitoneal
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No Duration Period; Positive Control Study (water maze)
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54596.0
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2012-03-20
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2017-02-10
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Added by
Madison Feshuk
on Apr 25, 2022
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