Tags

Type your tag names separated by a space and hit enter

Effects of the competitive N-methyl-D-aspartate antagonist CGP 37849 and its ethylester CGP 39551 on N-methyl-D-aspartate-evoked whole-cell currents in cultured spinal neurones and on vestibular stimulation-induced seizures in EL mice.
Arzneimittelforschung. 1998 Dec; 48(12):1121-5.A

Abstract

The competitive N-methyl-D-aspartate (NMDA) antagonist DL-2-amino-4-methyl-5-phosphono-3-pentenoic acid (CAS 127910-31-0, 4-methyl-APPA, CGP 37849) and its ethyl ester (CAS 127910-32-1, CGP 39551) potently block NMDA-evoked whole-cell current on mouse spinal neurones in primary dissociated cell cultures with IC50 (+/- SE) values of 189 +/- 9 nmol/l (CGP 37849) and 2100 +/- 220 nmol/l (CGP 39551), respectively. The compounds dose-dependently blocked vestibular stimulation-induced convulsions in EL mice, 2 h after oral administration, with ED50 (95% CI) values of 135 (78-236) mumol/kg (CGP 37849) and 65 (45-94) mumol/kg (CGP 39551). In male Swiss albino mice, performance in the step-through passive avoidance procedure was dose-dependently impaired with ED50 (95% CI) values of 85 (56-157) mumol/kg (CGP 37849) and 27 (18-42) mumol/kg (CGP 39551). In addition performance of these animals in the rotarod test of motor coordination was impaired, 2 h after oral administration of CGP 39551, with an ED50 (95% CI) of 142 (100-201) mumol/kg. These findings demonstrate anticonvulsant activity in these potent NMDA antagonists after oral administration with CGP 39551 possessing greater relative potency. However, the unfavourable ratio of therapeutic dose versus dose inducing memory or motor impairment supports the prevailing notion that such adverse effects of the presently available compounds preclude the use of NMDA antagonists as long-term therapies.

Authors+Show Affiliations

Laboratory of Neurochemistry and Behaviour, Born-Bunge Foundation, University of Antwerp (UIA), Belgium.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9893924

Citation

D'Hooge, R, et al. "Effects of the Competitive N-methyl-D-aspartate Antagonist CGP 37849 and Its Ethylester CGP 39551 On N-methyl-D-aspartate-evoked Whole-cell Currents in Cultured Spinal Neurones and On Vestibular Stimulation-induced Seizures in EL Mice." Arzneimittel-Forschung, vol. 48, no. 12, 1998, pp. 1121-5.
D'Hooge R, Raes A, Hiramatsu M, et al. Effects of the competitive N-methyl-D-aspartate antagonist CGP 37849 and its ethylester CGP 39551 on N-methyl-D-aspartate-evoked whole-cell currents in cultured spinal neurones and on vestibular stimulation-induced seizures in EL mice. Arzneimittelforschung. 1998;48(12):1121-5.
D'Hooge, R., Raes, A., Hiramatsu, M., Mori, A., Van Bogaert, P. P., & De Deyn, P. P. (1998). Effects of the competitive N-methyl-D-aspartate antagonist CGP 37849 and its ethylester CGP 39551 on N-methyl-D-aspartate-evoked whole-cell currents in cultured spinal neurones and on vestibular stimulation-induced seizures in EL mice. Arzneimittel-Forschung, 48(12), 1121-5.
D'Hooge R, et al. Effects of the Competitive N-methyl-D-aspartate Antagonist CGP 37849 and Its Ethylester CGP 39551 On N-methyl-D-aspartate-evoked Whole-cell Currents in Cultured Spinal Neurones and On Vestibular Stimulation-induced Seizures in EL Mice. Arzneimittelforschung. 1998;48(12):1121-5. PubMed PMID: 9893924.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of the competitive N-methyl-D-aspartate antagonist CGP 37849 and its ethylester CGP 39551 on N-methyl-D-aspartate-evoked whole-cell currents in cultured spinal neurones and on vestibular stimulation-induced seizures in EL mice. AU - D'Hooge,R, AU - Raes,A, AU - Hiramatsu,M, AU - Mori,A, AU - Van Bogaert,P P, AU - De Deyn,P P, PY - 1999/1/20/pubmed PY - 1999/1/20/medline PY - 1999/1/20/entrez SP - 1121 EP - 5 JF - Arzneimittel-Forschung JO - Arzneimittelforschung VL - 48 IS - 12 N2 - The competitive N-methyl-D-aspartate (NMDA) antagonist DL-2-amino-4-methyl-5-phosphono-3-pentenoic acid (CAS 127910-31-0, 4-methyl-APPA, CGP 37849) and its ethyl ester (CAS 127910-32-1, CGP 39551) potently block NMDA-evoked whole-cell current on mouse spinal neurones in primary dissociated cell cultures with IC50 (+/- SE) values of 189 +/- 9 nmol/l (CGP 37849) and 2100 +/- 220 nmol/l (CGP 39551), respectively. The compounds dose-dependently blocked vestibular stimulation-induced convulsions in EL mice, 2 h after oral administration, with ED50 (95% CI) values of 135 (78-236) mumol/kg (CGP 37849) and 65 (45-94) mumol/kg (CGP 39551). In male Swiss albino mice, performance in the step-through passive avoidance procedure was dose-dependently impaired with ED50 (95% CI) values of 85 (56-157) mumol/kg (CGP 37849) and 27 (18-42) mumol/kg (CGP 39551). In addition performance of these animals in the rotarod test of motor coordination was impaired, 2 h after oral administration of CGP 39551, with an ED50 (95% CI) of 142 (100-201) mumol/kg. These findings demonstrate anticonvulsant activity in these potent NMDA antagonists after oral administration with CGP 39551 possessing greater relative potency. However, the unfavourable ratio of therapeutic dose versus dose inducing memory or motor impairment supports the prevailing notion that such adverse effects of the presently available compounds preclude the use of NMDA antagonists as long-term therapies. SN - 0004-4172 UR - https://www.unboundmedicine.com/medline/citation/9893924/Effects_of_the_competitive_N_methyl_D_aspartate_antagonist_CGP_37849_and_its_ethylester_CGP_39551_on_N_methyl_D_aspartate_evoked_whole_cell_currents_in_cultured_spinal_neurones_and_on_vestibular_stimulation_induced_seizures_in_EL_mice_ L2 - https://medlineplus.gov/seizures.html DB - PRIME DP - Unbound Medicine ER -