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Pharmacological specificity of the discriminative stimulus properties of 2-amino-4,5-(1,2-cyclohexyl)-7-phosphono-heptanoic acid (NPC 12626), a competitive N-methyl-D-aspartate receptor antagonist.
J Pharmacol Exp Ther. 1993 Feb; 264(2):845-53.JP

Abstract

A drug discrimination based upon the competitive N-methyl-D-aspartate (NMDA) antagonist 2-amino-4,5-(1,2-cyclohexyl)-7-phosphonoheptanoic acid (NPC 12626) was assessed for pharmacological specificity. Adult male Sprague-Dawley rats were trained to discriminate 20 mg/kg i.p. of NPC 12626 from saline under a standard two-lever fixed ratio 32 schedule of food reinforcement. Stimulus generalization tests were conducted to examine the similarities and differences between NPC 12626, its active (2R,4R,5S) enantiomer NPC 17742, other competitive and noncompetitive NMDA antagonists and a number of drugs representative of other classes. During test sessions, the competitive NMDA antagonists NPC 12626, CGS 19755, [1-(cis-2-carboxypiperidine-4-yl)- methyl-1-phosphonic acid], NPC 17742, CSP 37849 [DL-(E)-2-amino-4-methyl-5-phosphono-3-pen-tenoic acid] and CPPene [D-3-(2-carboxypiperazin-4-yl)-1-propenyl-1-phosphonic acid] all completely substituted for the training dose of NPC 12626 with ED50 values of 18.1, 2.3, 2.1, 0.8 and 0.8 mg/kg, respectively. In contrast, drugs that failed to substitute for NPC 12626 included (+)-amphetamine, baclofen, chlorpromazine, dextromethorphan, diazepam, dizocilpine (MK-801), imipramine, (-)-ketocyclazocine, L-N6-phenylisopropyladenosine, methocarbamol, morphine, muscimol, phenytoin, physostigmine and valproate. These results provide evidence that the NPC 12626 discriminative stimulus is unique and specific, shared fully only by its active enantiomer NPC 17742 and other competitive NMDA antagonists. This specificity provides further support for the hypothesis of NMDA receptor mediation of NPC 12626 discrimination, and suggests that this is a useful model to evaluate behavioral effects of competitive NMDA antagonists.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond.No affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8437128

Citation

Bobelis, D J., and R L. Balster. "Pharmacological Specificity of the Discriminative Stimulus Properties of 2-amino-4,5-(1,2-cyclohexyl)-7-phosphono-heptanoic Acid (NPC 12626), a Competitive N-methyl-D-aspartate Receptor Antagonist." The Journal of Pharmacology and Experimental Therapeutics, vol. 264, no. 2, 1993, pp. 845-53.
Bobelis DJ, Balster RL. Pharmacological specificity of the discriminative stimulus properties of 2-amino-4,5-(1,2-cyclohexyl)-7-phosphono-heptanoic acid (NPC 12626), a competitive N-methyl-D-aspartate receptor antagonist. J Pharmacol Exp Ther. 1993;264(2):845-53.
Bobelis, D. J., & Balster, R. L. (1993). Pharmacological specificity of the discriminative stimulus properties of 2-amino-4,5-(1,2-cyclohexyl)-7-phosphono-heptanoic acid (NPC 12626), a competitive N-methyl-D-aspartate receptor antagonist. The Journal of Pharmacology and Experimental Therapeutics, 264(2), 845-53.
Bobelis DJ, Balster RL. Pharmacological Specificity of the Discriminative Stimulus Properties of 2-amino-4,5-(1,2-cyclohexyl)-7-phosphono-heptanoic Acid (NPC 12626), a Competitive N-methyl-D-aspartate Receptor Antagonist. J Pharmacol Exp Ther. 1993;264(2):845-53. PubMed PMID: 8437128.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacological specificity of the discriminative stimulus properties of 2-amino-4,5-(1,2-cyclohexyl)-7-phosphono-heptanoic acid (NPC 12626), a competitive N-methyl-D-aspartate receptor antagonist. AU - Bobelis,D J, AU - Balster,R L, PY - 1993/2/1/pubmed PY - 1993/2/1/medline PY - 1993/2/1/entrez SP - 845 EP - 53 JF - The Journal of pharmacology and experimental therapeutics JO - J. Pharmacol. Exp. Ther. VL - 264 IS - 2 N2 - A drug discrimination based upon the competitive N-methyl-D-aspartate (NMDA) antagonist 2-amino-4,5-(1,2-cyclohexyl)-7-phosphonoheptanoic acid (NPC 12626) was assessed for pharmacological specificity. Adult male Sprague-Dawley rats were trained to discriminate 20 mg/kg i.p. of NPC 12626 from saline under a standard two-lever fixed ratio 32 schedule of food reinforcement. Stimulus generalization tests were conducted to examine the similarities and differences between NPC 12626, its active (2R,4R,5S) enantiomer NPC 17742, other competitive and noncompetitive NMDA antagonists and a number of drugs representative of other classes. During test sessions, the competitive NMDA antagonists NPC 12626, CGS 19755, [1-(cis-2-carboxypiperidine-4-yl)- methyl-1-phosphonic acid], NPC 17742, CSP 37849 [DL-(E)-2-amino-4-methyl-5-phosphono-3-pen-tenoic acid] and CPPene [D-3-(2-carboxypiperazin-4-yl)-1-propenyl-1-phosphonic acid] all completely substituted for the training dose of NPC 12626 with ED50 values of 18.1, 2.3, 2.1, 0.8 and 0.8 mg/kg, respectively. In contrast, drugs that failed to substitute for NPC 12626 included (+)-amphetamine, baclofen, chlorpromazine, dextromethorphan, diazepam, dizocilpine (MK-801), imipramine, (-)-ketocyclazocine, L-N6-phenylisopropyladenosine, methocarbamol, morphine, muscimol, phenytoin, physostigmine and valproate. These results provide evidence that the NPC 12626 discriminative stimulus is unique and specific, shared fully only by its active enantiomer NPC 17742 and other competitive NMDA antagonists. This specificity provides further support for the hypothesis of NMDA receptor mediation of NPC 12626 discrimination, and suggests that this is a useful model to evaluate behavioral effects of competitive NMDA antagonists. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/8437128/Pharmacological_specificity_of_the_discriminative_stimulus_properties_of_2_amino_45__12_cyclohexyl__7_phosphono_heptanoic_acid__NPC_12626__a_competitive_N_methyl_D_aspartate_receptor_antagonist_ L2 - http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=8437128 DB - PRIME DP - Unbound Medicine ER -