Synthesis and NMD A Antagonistic Properties of the Enantiomers of 4‐(3‐phosphonopropyl)piperazine‐2‐carboxylic acid (CPP) and of the unsaturated analogue (E)‐4‐(3‐phosphonoprop‐2‐enyl)piperazine‐2‐carboxylic acid (CPP‐ene)

Abstract

The ( R ) -and (S)-enantiomers of 4-(3-phosphonopropyl)piperazine-2-carboxylic acid (D-and L-CPP, resp.; 15 and 16, resp.), and of its unsaturated analogue (E)-4-(3-phosphonoprop-2-enyl)piperazine-2-carboxylic acid (D-and L-CPP-ene, resp.; 13 and 14, resp.) were prepared. The absolute configuration of the enantiomers was determined by a chemical correlation of the menthyl ester 7 with o-asparagine. The affinity of these derivatives for the NMDA receptor was determined by displacement of [3H]CPP in rat cerebral cortical membranes. In two functional tests (the frog hemisected spinal cord preparation and the sodium efflux test from rat brain slices), o-CPP-ene appears to be the most potent, enantiomerically pure, competitive NMDA antagonist known to date.

Effects of NMDA receptor channel blockade on aggression in isolated male mice

“…For the present study, NMDA receptor channel blockers were tested along with the competitive NMDA receptor antagonist D-CPPene, which represented an alternative approach for reducing activity of NMDA receptor complex. D-CPPene (SDZ EAA 494) was selected because it is among the most potent, systemically active compounds available of this type [Aebischer et al, 1989;Lowe et al, 1994]. PCP and dizocilpine ((+)MK-801) were selected as representative PCP-like high-affinity noncompetitive antagonists [Wong et al, 1986].…”

A comparison between the non-competitive NMDA antagonist dizocilpine (MK-801) and the competitive NMDA antagonist D-CPPene with regard to dopamine turnover and locomotor-stimulatory properties in mice

“…Taken together, the above mentioned data suggest that locomotor stimulation following treatment with noncompetitive NMDA antagonists partly is mediated through activation of central catecholaminergic systems, whereas locomotor stimulation following competitive NMDA antagonists is not. The purpose of the present investigation was to compare the PCP-like, non-competitive NMDA antagonist dizocilpine (Wong et al, 1986) to the competitive NMDA antagonist D-CPPene (Aebischer et al, 1989), with regard to both central DA turnover and locomotor stimulatory properties in mice.…”

Behavioural and neurochemical adaptations to nicotine in rats: influence of NMDA antagonists

“…The experiments have been carried out with lower doses of dizocilpine than those used in previous work (Shoaib & Stolerman, 1992b;1992c) and with the competitive NMDA antagonist D-CPPene (SDZ EAA 494; 3-(2-carboxy-piperazin4yl)-1-propenyl-1-phosphonic acid) described by Aebischer et al (1989). In addition, in view of the importance of dopamine in mediating the effects of nicotine on stimulating locomotor activity, some of the studies were carried out with determinations of the extracellular concentration of dopamine, using in vivo microdialysis, in parallel with behavioural measurements.…”