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Biomedical subjects

T Honoré

Publications and source records attributed to T Honoré.

At least 19 recordsLinked to original sources
PubMed2006

Effects of the length of crosslink chain on poly(2-hydroxyethyl methacrylate) (pHEMA) swelling and biomechanical properties.

Polymers are widely used in medicine for vascular prostheses, bone substitutes, and devices for controlled release. Among these polymers, poly(2-hydroxyethyl methacrylate) (pHEMA) is the most employed. To confer particular properties, pHEMA can be copolymerized with other monomers or in the presence of plasticizers or crosslinking agents. The influence of the length of crosslink chains on swelling, surface rugosity, hardness, and stiffness of crosslinked pHEMA were studied by several techniques, including fractal analysis and AFM. Four crosslinking agents (divinyl benzene, DVB; ethylene glycol dimethacrylate, EGDMA; tetraethylene glycol diacrylate, TEGDA; and polyethylene glycol diacrylate, PEGDA) were added to the bulk polymerization mixture. Only linear and PEGDA-pHEMA presented a significant decrease in surface roughness confirmed by fractal analysis. Differences in hardness and biomechanical properties were evidenced on dried polymers but the highest differences were exhibited for hydrated pHEMA. Correlations between the length of the crosslink chain and hardness or stiffness of hydrated crosslinked pHEMA were evidenced. TEGDA and PEGDA appeared to be the two most suitable crosslinking agents for controlled release of bioactive molecules in bone.

Biocompatible Materials↗
PubMed1998

Different effects of phospholipase A2 on agonist binding to hippocampal, cortical and recombinant homomeric alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors.

Secretory phospholipase A2 (sPLA2) has been reported to modulate agonist and antagonist binding to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors. Here we report that in hippocampal membranes sPLA2 increases the affinity of [3H]AMPA binding whereas in cortical membranes the affinity of binding is decreased. To test whether these results are due to the interaction of sPLA2 with different AMPA receptor subunits we used membranes from BHK cells expressing homomeric GluR1, GluR2 or GluR4 receptors. Pretreatment with the enzyme had no effect on [3H]AMPA binding to any of the homomeric receptors. We interpret these data to suggest that sPLA2 does not act directly at the AMPA receptor. Instead, sPLA2 may interact with a receptor-associated protein present in brain but not in BHK cells and this interaction may exert different effects in cortex and hippocampus.

Animals↗
PubMed1997

High-affinity binding sites for 125I-labelled pancreatic secretory phospholipase A2 in rat brain.

Porcine pancreatic secretory phospholipase A2 (ppsPLA2) has been shown to modulate agonist and antagonist binding to alpha-amino-3-hydroxy-5-methylisoxazolepropionate (AMPA) receptors and to effect neurotransmission in the central nervous system (CNS). To further elucidate the mechanism of action of ppsPLA2 in the CNS, the binding profile of 125I-labelled ppsPLA2 to rat whole-brain membranes was assessed. Two classes of calcium-dependent binding sites were detected using unlabelled ppsPLA2 as a displacer with IC50 values of 3 and 217 nM. Similar values were obtained for [125I]ppsPLA2 binding to membranes prepared from isolated cortical and hippocampal rat brain regions. [125I]ppsPLA2 binding displayed bell-shaped concentration-dependence curves to Ca2+, Zn2 + and pH. Binding was not inhibited by AMPA, the false substrate, oleoyloxyethyl phosphocholine (OOPC), or by BSA-galactose or wheat germ agglutinin. [125I]ppsPLA2 binding was reduced by treatment of the rat brain membranes with mercaptoethanol and proteinase K treatment or by their pre-incubation at 95 degrees C. These results show a different binding profile to the previously characterised snake venom sPLA2 N-type receptors and suggest the existence of novel class of sPLA2 N-type binding sites.

Animals↗
PubMed1996

Brain glutamate transporter proteins form homomultimers.

Removal of excitatory amino acids from the extracellular fluid is essential for synaptic transmission and for avoiding excitotoxicity. The removal is accomplished by glutamate transporters located in the plasma membranes of both neurons and astroglia. The uptake system consists of several different transporter proteins that are carefully regulated, indicating more refined functions than simple transmitter inactivation. Here we show by chemical cross-linking, followed by electrophoresis and immunoblotting, that three rat brain glutamate transporter proteins (GLAST, GLT and EAAC) form homomultimers. The multimers exist not only in intact brain membranes but also after solubilization and after reconstitution in liposomes. Increasing the cross-linker concentration increased the immunoreactivity of the bands corresponding to trimers at the expense of the dimer and monomer bands. However, the immunoreactivities of the dimer bands did not disappear, indicating a mixture of dimers and trimers. GLT and GLAST do not complex with each other, but as demonstrated by double labeling post-embedding electron microscopic immunocytochemistry, they co-exist side by side in the same astrocytic cell membranes. The oligomers are held together noncovalently in vivo. In vitro, oxidation induces formation of covalent bonds (presumably -S-S-) between the subunits of the oligomers leading to the appearance of oligomer bands on SDS-polyacrylamide gel electrophoresis. Immunoprecipitation experiments suggest that GLT is the quantitatively dominant glutamate transporter in the brain. Radiation inactivation analysis gives a molecular target size of the functional complex corresponding to oligomeric structure. We postulate that the glutamate transporters operate as homomultimeric complexes.

ATP-Binding Cassette Transporters↗
PubMed1996

Pharmacology and regional distribution of the binding of 6-[3H]nitro-7-sulphamoylbenzo[f]-quinoxaline-2,3-dione to rat brain.

6-Nitro-7-sulphamoylbenzo[f]quinoxaline-2,3-dione (NBQX) is a competitive antagonist selective for alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors. Here we report the pharmacological characteristics and anatomical distribution of [3H]NBQX binding to rat brain. The association rate of [3H]NBQX to rat cerebrocortical membranes was rapid, with peak binding occurring within 10 min at 0 degree C. The off-rate was also rapid, with near-complete dissociation of the radioligand within 5 min of addition of 1 mM unlabelled L-glutamate. [3H]NBQX bound to a single class of sites with KD and Bmax values of 47 nM and 2.6 pmol mg-1 of protein, respectively. The rank order of inhibition of [3H]NBQX binding by AMPA receptor ligands was NBQX > > 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) > or = (S)-5-fluorowillardiine > or = AMPA > > L-glutamate. The chaotrope KSCN had no effect on the IC50 value of unlabelled NBQX displacement of [3H]NBQX binding. The kainate receptor-selective ligands NS102 and kainate were only very weak displacers. It is interesting that NBQX and CNQX displaced significantly more [3H]NBQX than any of the agonists tested. Autoradiographic analysis of the binding of [3H]NBQX to coronal sections showed a distribution compatible with that of [3H]AMPA binding. These data indicate that [3H]NBQX provides a useful novel tool to characterise the antagonist binding properties of AMPA receptors.

Animals↗
PubMed1995

Phospholipase A2 down-regulates the affinity of [3H]AMPA binding to rat cortical membranes.

The effects of exogenous phospholipase A2 on the binding of alpha-[3H]amino-3-hydroxy-5-methylisoxazole-4-propionate ([3H]AMPA) to rat cortical membranes in the presence of the chaotrope potassium thiocyanate were assessed. Pretreatment of membranes with secretory phospholipase A2 (sPLA2) elicited a concentration-dependent decrease in specific [3H]AMPA binding due mainly to a decrease in affinity (KD). This observation, together with protease inhibitor and western blot evidence, suggest that the sPLA2 effect is not due to proteolysis. The sPLA2-evoked decrease was temperature and calcium dependent. Inclusion of the specific inhibitor oleoyloxyethyl phosphocholine or preincubation of the enzyme with reducing agents to degrade its secondary structure significantly reduced the sPLA2 inhibition. These results suggest that the effects of sPLA2 arise from an enzymatic action rather than a competitive interaction at the AMPA binding site. However, arachidonic acid, a major metabolite of sPLA2 action, did not cause a similar decrease in the affinity of [3H]AMPA binding. In contrast to the effects on [3H]AMPA binding, sPLA2 caused an increase in [3H]CNQX binding, which is in accordance with the functionality of the AMPA receptor complex. These results suggest that sPLA2 may play a role in the physiological and pathophysiological regulation of AMPA receptors.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1995

Anticonvulsant, anxiolytic and discriminative effects of the AMPA antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX).

The anticonvulsant effects of 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX), phencyclidine (PCP) and diazepam against audiogenic seizures in DBA/2 mice and against seizures induced by methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) in NMRI mice were compared. Motor impairment was assessed in a rotarod apparatus in DBA/2 as well as NMRI mice. At 30 min after i.p. administration, NBQX was as effective as PCP and diazepam in protecting against audiogenic seizures and had a therapeutic ratio slightly higher than diazepam's and 7-fold higher than PCP's. Whereas diazepam was fully effective, NBQX and PCP were both ineffective against seizures induced by DMCM 30 min after i.p. administration. The anticonvulsant potential and motor-impairing effects of NBQX were evaluated further by the i.p. and the i.v. routes at different time points after administration. At all pretreatment intervals, NBQX protected against audiogenic seizures more potently than it produced motor impairment. NBQX administered i.p. protected against DMCM-induced seizures when given 15 min but not 5 min before testing, whereas after i.v. administration NBQX produced anticonvulsant and motor-impairing effects in the same dose range. NBQX only slightly and non-dose-dependently attenuated the discriminative effects of pentylenetetrazole in rats, showing a limited anxiolytic potential. NBQX produced no PCP-like or morphine-like discriminative effects in rats, suggesting lack of PCP or opiate-like subjective effects. These data demonstrate that NBQX has anticonvulsant effects, has limited anxiolytic effects, and does not produce subjective effects of PCP or opiate type.

Acoustic Stimulation↗
PubMed1993

Characterization of the metabotropic glutamate receptor in mouse cerebellar granule cells: lack of effect of 2,3-dihydroxy-6-nitro-7-sulphamoylbenzo(F)-quinoxaline (NBQX).

The ability of excitatory amino acids to stimulate phosphoinositide hydrolysis in mouse cerebellar granule cells was characterized. Quisqualic acid (EC50 = 2 microM), ibotenic acid (EC50 = 15 microM), kainic acid (EC50 = 30 microM), glutamate (EC50 = 51 microM) and (1S,3R)-1-amino-cyclo-pentane-1,3-dicarboxylic acid (t-ACPD) (EC50 = 175 microM) dose-dependently stimulated phosphoinositide hydrolysis. The stimulation of phosphoinositide hydrolysis was dose-dependently blocked by 2-amino-3-phosphonopropionic acid (L-AP3) and pertussis toxin, but was unaffected by other excitatory amino acid agonists or antagonists. These data suggest that the pharmacology of excitatory amino acid-stimulated phosphoinositide hydrolysis in the mouse cerebellar granule cells is mediated through the G protein coupled metabotropic glutamate receptor. The overall pharmacology of the metabotropic receptor present in mouse cerebellar granule cells differs from that of previously reported tissue preparations such as rat cerebellar granule cells. In addition, the effect of the alpha-amino-3-hydroxyl-5-methyl-1-isoxazole-4-propionic acid (AMPA) receptor antagonist, 2,3-dihydroxy-6-nitro-7-sulphamoylbenzo(F)quinoxaline (NBQX), on excitatory amino acid-stimulated phosphoinositide hydrolysis was also examined. NBQX was without effect on either basal phosphoinositide hydrolysis or excitatory amino acid-stimulated phosphoinositide hydrolysis, suggesting that the neuroprotective effect of NBQX is not mediated through the metabotropic glutamate receptor.

Alanine↗
PubMed1992

Novel functional M1 selective muscarinic agonists. 2. Synthesis and structure-activity relationships of 3-pyrazinyl-1,2,5,6-tetrahydro-1-methylpyridines. Construction of a molecular model for the M1 pharmacophore.

A series of 3-(3-substituted-pyrazinyl)-1,2,5,6-tetrahydro-1-methylpyridines were synthesized and found to have high affinity for central muscarinic receptors. The ability of some of these compounds to inhibit the electrically stimulated twitch of the guinea pig vas deferens indicated that the compounds were M1 agonists. M1 agonist activity was related to the length of the side chain attached to the pyrazine ring, with maximal activity being obtained with the hexyloxy side chain. The (hexyloxy)pyrazine 3f lacked M2 agonist activity as it failed to affect the guinea pig atria and was also relatively devoid of M3 agonist activity as determined by its lack of tremorogenic and sialogogic effects in mice. A comparison of the M1 agonist efficacy of these pyrazines and related 1,2,5-thiadiazoles and 1,2,5-oxadiazoles suggested that M1 efficacy was related to the magnitude of electrostatic potential located over the nitrogens of the respective heterocycles. The heteroatom directly attached to the 3 position of the pyrazine or 1,2,5-thiadiazole heterocycle markedly influenced the M1 efficacy of the compounds by determining the energetically favorably conformers for rotation about the bond connecting the tetrahydropyridyl ring and the heterocycle. A three-dimensional model for the M1-activating pharmacophore was proposed based on computational studies and the model of the muscarinic pharmacophore proposed by Schulman.

Animals↗
PubMed1992

Novel functional M1 selective muscarinic agonists. Synthesis and structure-activity relationships of 3-(1,2,5-thiadiazolyl)-1,2,5,6-tetrahydro-1-methylpyridines .

A series of novel 3-(3-substituted-1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahydro- 1-methylpyridines (substituted-TZTP; 5a-l, 7a-h, 8, 9c-n, 11, 13j) were synthesized and tested for central muscarinic cholinergic receptor affinity by using [3H]-oxotremorine-M (Oxo-M) and [3H]-pirenzepine (Pz) as ligands. The potency and efficacy of the compounds for the pharmacological defined M1 and M2 muscarinic receptors were determined on isolated electrically stimulated rabbit vas deferens and on spontaneously beating isolated guinea pig atria, respectively. Selected compounds were also tested for M3 activity in the isolated guinea pig ileum. The C1-8 alkoxy-TZTP 5a-l analogues all displaced [3H]-Oxo-M and [3H]-Pz with low nanomolar affinity. Depicting chain length against Oxo-M binding and against Pz binding the unbranched C1-8 alkoxy-TZTP (5a-h) derivatives produced U-shaped curves with butoxy- (5d) and (pentyloxy)-TZTP (5e) as the optimum chain length, respectively. This U-shaped curve was also seen in the ability of the compounds 5a-h to inhibit the twitch height in the vas deferens preparation. The (pentyloxy)- (5e) and the (hexyloxy)-TZTP (5f) analogues produced an over 90% inhibition of the twitch height with IC50 values in the low picomolar range. In both the atria and in the ileum preparations 5f had low efficacy and potency. With the (alkylthio)-TZTP (7a-h) analogues the structure-activity relationship was similar to the one observed with the alkoxy (5a-h) analogues, but generally 7a-h had higher receptor affinity and was more potent than the corresponding 5a-h. However, the C3-8 alkyl-TZTP (9c,e,g,h) analogues had 10-100 times lower affinity for the central muscarinic receptors than the corresponding alkoxy and alkylthio derivatives, and their efficacy in the vas deferens preparation was too low to obtain IC50 values. The unsubstituted TZTP (11) compound was a potent but nonselective muscarinic agonist. The two 3-(3-butoxy/(hexyloxy)-1,2,5-oxadiazol-4-yl)-1,2,5,6-tetrahy dro-1- methylpyridines (butoxy/hexyloxy)-OZTP; 19a/b) were also synthesized and tested. Both 19a and 19b had much lower affinity for the central muscarinic receptors than 5d and 5f, and the efficacy of 19a,b was too low to give IC50 values in the vas deferens preparation. Therefore, the C5-6 (alkyloxy)/(alkylthio)-TZTP's represent a unique series of potent functional M1 selective muscarinic agonists.

Animals↗
PubMed1992

Inhibition of cisplatin-induced emesis in ferrets by the non-NMDA receptor antagonists NBQX and CNQX.

The excitatory amino acid (EAA) receptor antagonists, 2,3-dihydroxy-6-nitro-7-sulphamoylbenzo(f)quinoxaline (NBQX) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), which preferentially block non-N-methyl-D-aspartate (non-NMDA) subtypes of EAA receptors, effectively inhibit cisplatin-induced emesis in ferrets. A high dose of cisplatin (10 mg/kg i.v.) was used which induced emesis in all saline-treated control ferrets. At 10 mg/kg i.v., NBQX totally prevented cisplatin-induced emesis in 5 of 6 ferrets and CNQX totally prevented emesis in 3 of 5 ferrets. By comparison, each of the 5-HT3 inhibitors, zacopride and ondansetron, at 1.0 mg/kg i.v. (a dose considered in the high therapeutic range for controlling emesis by these compounds), totally prevented emesis in 2 of 5 ferrets. It is concluded that non-NMDA antagonists effectively inhibit cisplatin-induced emesis. They are potential antiemetic compounds, alone or in combination with 5-HT3 antagonists or other more conventional drugs of choice.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1992

Protection against ischemic hippocampal CA1 damage in the rat with a new non-NMDA antagonist, NBQX.

Two glutamate antagonists were tested in a rat model of complete, transient cerebral ischemia. Six days after 10 min ischemia the mean loss of hippocampal CA1 pyramidal neurones was 73%. Administration of the AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) antagonist NBQX (2,3-dihydro-6-nitro-7-sulfamoyl-benzo(F)quinoxaline) reduced the pyramidal neurone loss to 1%, 11% and 15%, when given before, immediately after or 1 h after ischemia, respectively. MK-801 (dizocilpine), a competitive NMDA antagonist gave no protection in this model. We suggest that the AMPA receptor transduction mechanisms are sensitized by ischemia and that the postischemic blockade of the main glutamatergic input to the CA1 cells with NBQX impairs the deleterious effect of "normal" postischemic excitatory transmission.

Animals↗
PubMed1992

Relief of experimental spasticity and anxiolytic/anticonvulsant actions of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline.

Spasticity is characterized by pathological overactivity in spinal stretch reflex circuits and may be associated with disturbances in excitatory amino acid-mediated transmission in the cord. A genetically determined syndrome of spasticity in the rat permits the quantitative evaluation of the antispastic effects of drugs by recording activity in the electromyogram (EMG) from a hind limb extensor muscle. In genetically spastic rats, systemic administration of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) antagonist, 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F) quinoxaline (NBQX), normalized pathologically increased EMG activity, whereas the AMPA agonist, alpha-amino-3-hydroxy-5-tertbutyl-4-isoxazolepropionate (ATPA), exacerbated the EMG measures of spasticity. The reflex mechanisms in the spinal cord can be studied in mice using EMG recordings from the tibial muscle (Hoffmann reflex) or from the plantar foot muscle (flexor reflex) after electrical stimulation of the tibial nerve. Systemic and i.t. administration of NBQX blocked Hoffmann reflexes in mice, leaving flexor reflexes unchanged. ATPA enhanced Hoffmann, and had no effect on flexor reflexes. The effects of NBQX on spinal reflexes were seen in doses which do not affect locomotor activity, but show anxiolytic and some antiepileptic activity in rodents. These data suggest that the design of novel muscle relaxant drugs acting at the AMPA subtype of glutamate receptors may be feasible.

Animals↗
PubMed1992

Excitatory amino acid receptor antagonist in murine motoneuron disease (the wobbler mouse).

Recent evidence has suggested a potential role for involvement of excitatory amino acids (EAA) in the pathogenesis of the neuron loss in motoneuron diseases. We have examined the ability of an antagonist of N-methyl-D-aspartate (NMDA) receptors to halt or retard the progression of neurological symptoms in a murine form of motoneuron disease. The wobbler mouse is an autosomal recessive mutant which develops progressive neurological symptoms secondary to motoneuron loss. Treatment of wobbler mice with the NMDA receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5, 10-imine maleate (MK-801) did not retard neurological deterioration as assessed by a semiquantitative clinical scale. We conclude that NMDA receptor activation is probably not involved in the pathogenesis of motoneuron loss in the wobbler mouse.

Amyotrophic Lateral Sclerosis↗
PubMed1991

Protection against post-ischemic behavioral pathology by the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX) in the gerbil.

The neuroprotective effects of NBQX (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline) were assessed on hippocampal CA1 neuronal loss and locomotor hyperactivity following transient bilateral carotid artery occlusion (BCAO) in the gerbil. NBQX, a selective blocker of the AMPA glutamate receptor subtype, was injected 1 h after 5 or 10 min BCAO, or sham surgery. Both 5 and 10 min ischemia produced equivalent hyperactivity 3 days post ischemia and CA1 neuronal loss on Day 4, while activity was unchanged in the sham-operated group. NBQX protected from both hippocampal damage and post-ischemic hyperactivity. These results demonstrate that NBQX can protect from behavioral pathology induced by global cerebral ischemia.

Animals↗
PubMed1991

The AMPA receptor antagonist NBQX has antiparkinsonian effects in monoamine-depleted rats and MPTP-treated monkeys.

Abnormally increased subthalamic nucleus output to the internal pallidal segment and the reticular part of the substantia nigra plays a critical pathophysiological role in the development of parkinsonism. Because synaptic transmission of subthalamic output is glutamatergic and mediated, in part, by the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) subtype of glutamate receptor, AMPA receptor antagonists may possess antiparkinsonian properties. We report that in monoamine-depleted rats, 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX) (Novo-Nordisk, Copenhagen, Denmark)--a selective antagonist of the AMPA subtype of glutamate receptor--suppressed muscular rigidity but had no effect on akinesia. NBQX microinjected into the subthalamic nucleus, internal pallidal segment, and reticular part of the substantia nigra, but not into the laterodorsal neostriatum of the rats, stimulated locomotor activity and reduced muscular rigidity. In aged Rhesus monkeys with bilateral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism, intramuscular NBQX produced clinically apparent improvement in akinesia, tremor, posture, and gross motor skills. NBQX also potentiated the antiparkinsonian effects of L-3,4-dihydroxyphenylalanine in both rats and monkeys. Blockade of excitatory synaptic transmission by AMPA receptor antagonists may provide a new therapeutic strategy for Parkinson's disease (PD).

Animals↗
PubMed1991

Synergism of the AMPA-antagonist NBQX and the NMDA-antagonist CPP with L-dopa in models of Parkinson's disease.

Degeneration of dopaminergic nigrostriatal neurons in Parkinson's disease results in an overactivity of excitatory glutamatergic projections from the subthalamic nucleus to the output nuclei of the basal ganglia resulting in rigidity and akinesia. In theory pharmacological blockade of these overactive systems should improve parkinsonian symptomatology. The selective AMPA-antagonist NBQX and the competitive NMDA-antagonist CPP are not effective in animal models of Parkinson's disease when given alone but ameliorate parkinsonian symptomatology and stimulate locomotor activity when co-administered with a threshold dose of L-Dopa. These synergistic effects are seen in the MPTP-treated (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) common marmoset and the rat with unilateral 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra. Therefore competitive NMDA and non-NMDA antagonists may offer a new therapeutic strategy for the treatment of Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗