Pharmacological characterisation and autoradiographic distribution of polyamine-sensitive [3H]ifenprodil binding sites in the rat brain

Dana, C; Bénavidès, J.; Schoemaker, Hans E.; Scatton, B.

doi:10.1016/0304-3940(91)90127-f

Cited by 42 publications

(13 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ifenprodil and SL 82 0715 have recently been reported to be potent com petitive antagonists of the polyamine modulatory site of the NMDA receptor in a number of biochemical models [29,30], For instance, in the presence of glutamate, polyamine-induced enhancement of 3H-TCP binding to rat forebrain membranes is blocked by these compounds which produce a rightward shift in the dose response curves for polyamines, suggesting competitive antago nism. That ifenprodil interacts with the polyamine mod ulatory site is further supported by binding studies dem onstrating that 3H-ifenprodil labels a high-affinity bind ing site in rat brain membranes or sections which is dis placeable by the polyamines spermine and spermidine [31,32]. The distribution of 3H-ifenprodil binding in rat brain sections matches closely that observed for NMDA receptors, with high densities in brain regions sensitive to hypoxia e.g.…”

Section: The Nm Da Receptor Complex and Its Pharmacologysupporting

confidence: 59%

“…The distribution of 3H-ifenprodil binding in rat brain sections matches closely that observed for NMDA receptors, with high densities in brain regions sensitive to hypoxia e.g. the hippocampus (dentate gyrus, stratum oriens and lucidum of CA| fields), superficial layers of the cerebral cortex and striatum [32],…”

Section: The Nm Da Receptor Complex and Its Pharmacologymentioning

confidence: 66%

See 1 more Smart Citation

N-Methyl-<i>D</i>-Aspartate Receptor Antagonists: A Novel Therapeutic Perspective for the Treatment of Ischemic Brain Injury

Scatton¹,

Carter²,

Bénavidès³

et al. 1991

Cerebrovasc Dis

View full text Add to dashboard Cite

Considerable experimental evidence suggests that excessive stimulation of the N-methyl-D-aspartate (NMDA) receptor subclass of glutamate receptors plays a pivotal role in initiating biochemical processes that lead to neuronal death during cerebral ischemia. Several NMDA receptor antagonists acting at the various sites within the NMDA receptor complex effectively attenuate the neuropathological consequences of brain ischemia in a wide variety of experimental models even when given after the ischemic insult. A number of new NMDA antagonists are currently in preclinical development and a few agents are in the early phases of clinical trials. The present review examines the case for this new. therapeutic perspective.

show abstract

Section: The Nm Da Receptor Complex and Its Pharmacologysupporting

confidence: 59%

Section: The Nm Da Receptor Complex and Its Pharmacologymentioning

confidence: 66%

N-Methyl-<i>D</i>-Aspartate Receptor Antagonists: A Novel Therapeutic Perspective for the Treatment of Ischemic Brain Injury

Scatton¹,

Carter²,

Bénavidès³

et al. 1991

Cerebrovasc Dis

View full text Add to dashboard Cite

show abstract

“…91,92 Although [ 3 H]ifenprodil primarily labels NMDA sites, it also binds to sites. [93][94][95] Utilization of the NMDA/polyamine modulatory sites as targets for drug intervention in epilepsy, is still in the early stages of research.…”

Section: Nmda Receptorsmentioning

confidence: 99%

Molecular targets for the rational design of antiepileptic drugs and related neuroprotective agents

Lin¹,

Kadaba²

1997

Med. Res. Rev.

View full text Add to dashboard Cite

“…1990;Beart et al, 1991;1992ab;Dana et al, 1991;Benavides et al, 1992;Mercer et al, 1993). Our laboratory has extended the range of available polyamine NMDA antagonists by describing a series of heterocyclic aminoalcohols (Figure 1), which, like ifenprodil and SL82.0715, fully inhibited all polyamine-sensitive binding of cerebral cortical membranes (Beart et al, 1992b;Mercer et al, 1993 (Beart et al, 1992b).…”

Section: (Eliprodil (+ )-(4-chlorophenyl)-4-[(4-fluorphenyl)mentioning

confidence: 99%

Blockade by polyamine NMDA antagonists related to ifenprodil of NMDA‐induced synthesis of cyclic GMP, increases in calcium and cytotoxicity in cultured neurones

Beart

Schousboe²,

Frandsen³

1995

British J Pharmacology

View full text Add to dashboard Cite

1 Antagonists acting at the polyamine site of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor, including a number of heterocyclic aminoalcohols related to ifenprodil, were investigated to establish their functional interaction at the NMDA receptor and their neuroprotective profile.2 In murine cultured neocortical neurones, NMDA (100 jiM)-stimulated production of guanosine 3':5'-cyclic monophosphate (cyclic GMP) was blocked by N-l([thienyl]-cyclohexyl)-piperidine (1 tiM) and by the nitric oxide (NO) synthase inhibitor N0-nitro-L-arginine (100 iM). Ifenprodil and structurally related heterocyclic aminoalcohols inhibited in a concentration-dependent manner the NMDAstimulated, NO-dependent production of cyclic GMP; rank potency order was: ifenprodil > 2309 BT > tibalosine > threo-tibalosine > 840S.3 All of the polyamine NMDA antagonists blocked NMDA (300 fiM)-stimulated increases in intracellular calcium concentrations as measured by changes in the fluorescence of pre-loaded fluo-3-acetoxy methyl ester. Rank potency order was: ifenprodil > 2309 BT > 840S > tibalosine > threotibalosine. 4 In a series of experiments to evaluate the effectiveness of the polyamine NMDA antagonists as blockers of NMDA-induced cytotoxicity, all of the drugs were found to inhibit the leakage of lactate dehydrogenase after the exposure of the murine neocortical cultures to NMDA (100 JM, 5 h). Rank potency order was: 2309 BT > ifenprodil > tibalosine > threo-tibalosine > 840S. 5 These results provide direct evidence that polyamine NMDA antagonists produce a functional blockade of the NMDA receptor complex. The heterocyclic aminoalcohols described herein, like ifenprodil, block NMDA-mediated elevation of intracellular NO and calcium, two key events in the excitotoxic cascade, and are cytoprotective.

show abstract

Pharmacological characterisation and autoradiographic distribution of polyamine-sensitive [3H]ifenprodil binding sites in the rat brain

Cited by 42 publications

References 5 publications

N-Methyl-<i>D</i>-Aspartate Receptor Antagonists: A Novel Therapeutic Perspective for the Treatment of Ischemic Brain Injury

N-Methyl-<i>D</i>-Aspartate Receptor Antagonists: A Novel Therapeutic Perspective for the Treatment of Ischemic Brain Injury

Molecular targets for the rational design of antiepileptic drugs and related neuroprotective agents

Blockade by polyamine NMDA antagonists related to ifenprodil of NMDA‐induced synthesis of cyclic GMP, increases in calcium and cytotoxicity in cultured neurones

Contact Info

Product

Resources

About