TY  - JOUR
AU  - Ping, Xingjie
AU  - Meyer, Michelle J.
AU  - Zahn, Nicolas M.
AU  - Golani, Lalit K.
AU  - Sharmin, Dishary
AU  - Pandey, Kamal P.
AU  - Revanian, Sepideh
AU  - Mondal, Prithu
AU  - Jin, Xiaoming
AU  - Arnold, Leggy A.
AU  - Cerne, Rok
AU  - Cook, James M.
AU  - Divović, Branka
AU  - Savić, Miroslav
AU  - Lippa, Arnold
AU  - Smith, Jodi L.
AU  - Witkin, Jeffrey M.
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4427
AB  - A series of imidazodiazepines has been developed that possess reduced sedative liabilities but retain efficacy in anticonvulsant screening models. The latest of these compounds, (5-(8-ethynyl-6-(pyridin-2-yl)-4H-benzo[f]imidazole[1,5-α][1,4]diazepin-3-yl) oxazole known as KRM-II-81) is currently awaiting advancement into the clinic. A deuterated structural analog (D5-KRM-II-81) was made as a potential backup compound and studied here in comparison to KRM-II-81. In the present study, both compounds significantly prevented seizures in mice induced by 6 Hz (44 mA) electrical stimulation without significantly altering motoric function on a rotarod after intraperitoneal administration. Both compounds also significantly prevented clonic seizures, tonic seizures, and lethality induced by pentylenetetrazol in mice when given orally. D5-KRM-II-81 had a slightly longer duration of action against clonic and tonic seizures than KRM-II-81. Oral administration of 100 mg/kg of either KRM-II-81 or D5-KRM-II-81 was significantly less disruptive of sensorimotor function in mice than diazepam (5 mg/kg, p.o.). The present report documents that D5-KRM-II-81 represents another in this series of imidazodiazepines with anticonvulsant activity at doses that do not impair sensorimotor function.
PB  - John Wiley and Sons Inc
T2  - Drug Development Research
T1  - Comparative anticonvulsant activity of the GABAkine KRM-II-81 and a deuterated analog
VL  - 84
IS  - 3
DO  - 10.1002/ddr.22042
ER  - 

@article{
author = "Ping, Xingjie and Meyer, Michelle J. and Zahn, Nicolas M. and Golani, Lalit K. and Sharmin, Dishary and Pandey, Kamal P. and Revanian, Sepideh and Mondal, Prithu and Jin, Xiaoming and Arnold, Leggy A. and Cerne, Rok and Cook, James M. and Divović, Branka and Savić, Miroslav and Lippa, Arnold and Smith, Jodi L. and Witkin, Jeffrey M.",
year = "2023",
abstract = "A series of imidazodiazepines has been developed that possess reduced sedative liabilities but retain efficacy in anticonvulsant screening models. The latest of these compounds, (5-(8-ethynyl-6-(pyridin-2-yl)-4H-benzo[f]imidazole[1,5-α][1,4]diazepin-3-yl) oxazole known as KRM-II-81) is currently awaiting advancement into the clinic. A deuterated structural analog (D5-KRM-II-81) was made as a potential backup compound and studied here in comparison to KRM-II-81. In the present study, both compounds significantly prevented seizures in mice induced by 6 Hz (44 mA) electrical stimulation without significantly altering motoric function on a rotarod after intraperitoneal administration. Both compounds also significantly prevented clonic seizures, tonic seizures, and lethality induced by pentylenetetrazol in mice when given orally. D5-KRM-II-81 had a slightly longer duration of action against clonic and tonic seizures than KRM-II-81. Oral administration of 100 mg/kg of either KRM-II-81 or D5-KRM-II-81 was significantly less disruptive of sensorimotor function in mice than diazepam (5 mg/kg, p.o.). The present report documents that D5-KRM-II-81 represents another in this series of imidazodiazepines with anticonvulsant activity at doses that do not impair sensorimotor function.",
publisher = "John Wiley and Sons Inc",
journal = "Drug Development Research",
title = "Comparative anticonvulsant activity of the GABAkine KRM-II-81 and a deuterated analog",
volume = "84",
number = "3",
doi = "10.1002/ddr.22042"
}

Ping, X., Meyer, M. J., Zahn, N. M., Golani, L. K., Sharmin, D., Pandey, K. P., Revanian, S., Mondal, P., Jin, X., Arnold, L. A., Cerne, R., Cook, J. M., Divović, B., Savić, M., Lippa, A., Smith, J. L.,& Witkin, J. M.. (2023). Comparative anticonvulsant activity of the GABAkine KRM-II-81 and a deuterated analog. in Drug Development Research
John Wiley and Sons Inc., 84(3).
https://doi.org/10.1002/ddr.22042

Ping X, Meyer MJ, Zahn NM, Golani LK, Sharmin D, Pandey KP, Revanian S, Mondal P, Jin X, Arnold LA, Cerne R, Cook JM, Divović B, Savić M, Lippa A, Smith JL, Witkin JM. Comparative anticonvulsant activity of the GABAkine KRM-II-81 and a deuterated analog. in Drug Development Research. 2023;84(3).
doi:10.1002/ddr.22042 .

Ping, Xingjie, Meyer, Michelle J., Zahn, Nicolas M., Golani, Lalit K., Sharmin, Dishary, Pandey, Kamal P., Revanian, Sepideh, Mondal, Prithu, Jin, Xiaoming, Arnold, Leggy A., Cerne, Rok, Cook, James M., Divović, Branka, Savić, Miroslav, Lippa, Arnold, Smith, Jodi L., Witkin, Jeffrey M., "Comparative anticonvulsant activity of the GABAkine KRM-II-81 and a deuterated analog" in Drug Development Research, 84, no. 3 (2023),
https://doi.org/10.1002/ddr.22042 . .