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45121522.DER.pdf
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45121522
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Amicarbazone
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129909-90-6
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114004
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Hense, S. (1997) BAY 31-4666 (MKH 3586) CNS-Safety Pharmacology After a Single Oral Administration in Mice: Lab Project Number: P 8011529: PH-25384: 107617. Unpublished study prepared by Bayer AG. 24 p.
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1997.0
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Amicarbazone: In a non-guideline study (MRID 45121522), a single dose of MKH 3586 (Amicarbazone; Lot/batch # 05362/0005; 98.4% a.i.), in a 0.5% aqueous tylose suspension (w/v) plus 0.4% Tween-80, was administered orally, in a dosing volume of 10 mL/kg, to 40 male HsdWin: NMRI mice/group at dose levels of 0, 1, 20 or 100 mg/kg/day. Control animals received an appropriate volume of vehicle without test substance. The following tests were performed (10 animals/test): (1) hot plate test (analgesia), 56°C at pretreatment, 30, 45, 60 and 120 min postdosing; (2) traction, balance rod and electroshock test (reduction of traction force, sensorimotor disturbances and anticonvulsive activity at 30, 40 and 50 minutes postdosing, respectively); (3) pentylenetetrazole test (pro- and anticonvulsive activity at 45 minutes postdosing; volume of pentylenetetrazole required to induce clonic seizure) and (4) hexobarbital test (potentiation or reduction of narcotic effects at 60 minutes postdosing, duration of anesthesia measured). The objective of this study was to assess the effects of a single oral administration of MKH 3586 on the central nervous system of mice.
At 100 mg/kg, mice showed increased (not significant unless noted) response times compared to controls to a nociceptive stimulus at 30 (incr. 24%), 45 (incr. 45%), 60 (p<=0.05; incr. 67%) and 120 (incr. 32%) minutes after dosing. 2/10 mice were observed to have reduced traction force and impaired motor coordination, compared to 0/10 in the controls and in the 1 and 20 mg/kg groups. An increased (p<=0.05) mean threshold dose of pentylenetetrazole was noted (incr. 16%) compared to controls, indicating an anticonvulsant effect by the test compound. Mice also were observed to exhibit sedation and partial ptosis approximately 20 minutes after treatment.
Following treatment with the test compound, all mice at all doses exhibited tonic convulsions in the electroshock test. Additionally, no treatment-related effects were observed on the duration of hexobarbital-induced anesthesia. There were no effects on the CNS of the 1 and 20 mg/kg mice in any test.
The data indicate that a single oral dose of MKH 3586 at 100 mg/kg causes minimal CNS functional impairment, characterized by increased reaction times to nociceptive stimuli, reduced traction force, impaired motor coordination, sedation, partial ptosis and a mild anticonvulsive effect.
The submitted study is classified as acceptable/non-guideline and satisfies the intended purpose of assessing the effects of a single oral administration of MKH 3586 on the central nervous system of mice.
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Neurotoxicity
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NA [81-9, Developmental neurotoxicity (use 870.3650 or 870.6300 instead of this)]
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Oral
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Treatment Duration: 1 Dose; gavage
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50559.0
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2005-12-14
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2006-06-30
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Added by
Madison Feshuk
on Apr 25, 2022
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