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Behavioral pharmacology of NPC 17742, a competitive N-methyl-D-aspartate (NMDA) antagonist.
J Pharmacol Exp Ther. 1993 Jun; 265(3):1055-62.JP

Abstract

The behavioral effects of the competitive N-methyl-D-aspartate (NMDA) antagonist 2R,4R,5S-2-amino-4,5-(1,2-cyclohexyl)-7-phosphonoheptanoate (NPC 17742) were compared with those of its parent compound, 2-amino-4,5-(1,2-cyclohexyl)-7-phosphonoheptanoate (NPC 12626), and other reference agents in a variety of operant-based tasks in rodents. In mice trained to lever press under a fixed-ratio (FR) 20 reinforcement schedule, NPC 17742 was 6.2 times more potent than NPC 12626 and equipotent with the competitive NMDA antagonist [E]-2-amino-4-methyl-5-phosphono-3-penteneoic acid (CGP 37849) in reducing rates of responding. NPC 17742 was also 3.5 and 4.5 times more potent than [+-]cis-4-phosphonomethyl-2-piperidine carboxylate (CGS 19755) and [+-] 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonate (CPP), respectively, and half as potent as 3SR, 4aRS, 6SR, 8aRS-6-(phosphonomethyl)-1,2,3,4,4a,5,6,7,8,8a- decahydroisoquinoline-3-carboxylate (LY 274614) in this paradigm. In rats trained to discriminate 4.0 mg/kg NPC 17742 from saline, NPC 17742 was 5.7 times more potent than NPC 12626 in substituting for NPC 17742. CGS 19755 also substituted for NPC 17742, but a maximum of only 50% NPC 17742 lever responding was observed after LY 274614 administration. In rats trained to lever press in a modified Geller-Seifter procedure, NPC 17742 and NPC 12626, like the benzodiazepine chlordiazepoxide, increased rates of punished responding. Neither tolerance nor sensitization to the anti-punishment effects were observed upon administration of NPC 17742 for 5 consecutive days. The results are consistent with NPC 17742 being a potent, systemically active compound whose behavioral effects are mediated through interaction with the NMDA receptor.(

ABSTRACT

TRUNCATED AT 250 WORDS)

Authors+Show Affiliations

Scios Nova Inc., Baltimore, Maryland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

8099615

Citation

Willetts, J, et al. "Behavioral Pharmacology of NPC 17742, a Competitive N-methyl-D-aspartate (NMDA) Antagonist." The Journal of Pharmacology and Experimental Therapeutics, vol. 265, no. 3, 1993, pp. 1055-62.
Willetts J, Clissold DB, Hartman TL, et al. Behavioral pharmacology of NPC 17742, a competitive N-methyl-D-aspartate (NMDA) antagonist. J Pharmacol Exp Ther. 1993;265(3):1055-62.
Willetts, J., Clissold, D. B., Hartman, T. L., Brandsgaard, R. R., Hamilton, G. S., & Ferkany, J. W. (1993). Behavioral pharmacology of NPC 17742, a competitive N-methyl-D-aspartate (NMDA) antagonist. The Journal of Pharmacology and Experimental Therapeutics, 265(3), 1055-62.
Willetts J, et al. Behavioral Pharmacology of NPC 17742, a Competitive N-methyl-D-aspartate (NMDA) Antagonist. J Pharmacol Exp Ther. 1993;265(3):1055-62. PubMed PMID: 8099615.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Behavioral pharmacology of NPC 17742, a competitive N-methyl-D-aspartate (NMDA) antagonist. AU - Willetts,J, AU - Clissold,D B, AU - Hartman,T L, AU - Brandsgaard,R R, AU - Hamilton,G S, AU - Ferkany,J W, PY - 1993/6/1/pubmed PY - 1993/6/1/medline PY - 1993/6/1/entrez SP - 1055 EP - 62 JF - The Journal of pharmacology and experimental therapeutics JO - J. Pharmacol. Exp. Ther. VL - 265 IS - 3 N2 - The behavioral effects of the competitive N-methyl-D-aspartate (NMDA) antagonist 2R,4R,5S-2-amino-4,5-(1,2-cyclohexyl)-7-phosphonoheptanoate (NPC 17742) were compared with those of its parent compound, 2-amino-4,5-(1,2-cyclohexyl)-7-phosphonoheptanoate (NPC 12626), and other reference agents in a variety of operant-based tasks in rodents. In mice trained to lever press under a fixed-ratio (FR) 20 reinforcement schedule, NPC 17742 was 6.2 times more potent than NPC 12626 and equipotent with the competitive NMDA antagonist [E]-2-amino-4-methyl-5-phosphono-3-penteneoic acid (CGP 37849) in reducing rates of responding. NPC 17742 was also 3.5 and 4.5 times more potent than [+-]cis-4-phosphonomethyl-2-piperidine carboxylate (CGS 19755) and [+-] 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonate (CPP), respectively, and half as potent as 3SR, 4aRS, 6SR, 8aRS-6-(phosphonomethyl)-1,2,3,4,4a,5,6,7,8,8a- decahydroisoquinoline-3-carboxylate (LY 274614) in this paradigm. In rats trained to discriminate 4.0 mg/kg NPC 17742 from saline, NPC 17742 was 5.7 times more potent than NPC 12626 in substituting for NPC 17742. CGS 19755 also substituted for NPC 17742, but a maximum of only 50% NPC 17742 lever responding was observed after LY 274614 administration. In rats trained to lever press in a modified Geller-Seifter procedure, NPC 17742 and NPC 12626, like the benzodiazepine chlordiazepoxide, increased rates of punished responding. Neither tolerance nor sensitization to the anti-punishment effects were observed upon administration of NPC 17742 for 5 consecutive days. The results are consistent with NPC 17742 being a potent, systemically active compound whose behavioral effects are mediated through interaction with the NMDA receptor.(ABSTRACT TRUNCATED AT 250 WORDS) SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/8099615/Behavioral_pharmacology_of_NPC_17742_a_competitive_N_methyl_D_aspartate__NMDA__antagonist_ L2 - http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=8099615 DB - PRIME DP - Unbound Medicine ER -