The competitive NMDA receptor antagonist SDZ 220-581 reverses haloperidol-induced catalepsy in rats.

Abstract

The present studies investigated whether SDZ 220-581 ((S)-alpha-amino 2'chloro-5-(phosphonomethyl)[1,1'-biphenyl]-3-propanoic acid), a potent, competitive antagonist at the NMDA glutamate receptor subtype, reversed haloperidol-induced catalepsy in rats, a widely used model of Parkinson's disease. SDZ 220-581 (0.32-3.2 mg/kg i.p.) dose- and time-dependently reduced the time spent in an abnormal position induced by haloperidol (1.0 mg/kg s.c.). Compared to other NMDA receptor antagonists the rank order of potency was MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine) > SDZ 220-581 > SDZ EAA 494 (D-CPPene: (S)-(E)-4-(3-phosphonoprop-2-enyl)-piperazine-2-carboxylic acid) > SDZ EAB 515 ((S)-alpha-amino-5-(phosphonomethyl)[1,1'-biphenyl]-3-propanoic acid). Since it has been demonstrate that SDZ 220-581 counters the effects of L-dihydroxyphenylalanine (L-DOPA) on the motor disturbances of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-pre-treated primates, the results suggest that the reversal of haloperidol-induced catalepsy by competitive NMDA receptor antagonists may not be predictive of efficacy in other models of Parkinson's disease.

• Authors: K H McAllister
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 314 Issue 3 Pg. 307-11 (Oct 31 1996) ISSN: 0014-2999 [Print] Netherlands
• PMID: 8957251 (Publication Type: Journal Article)

Chemical References

• Antipsychotic Agents
• Biphenyl Compounds
• Excitatory Amino Acid Antagonists
• Neuroprotective Agents
• Propionates
• Receptors, N-Methyl-D-Aspartate
• alpha-amino-2'-chloro-5-(phosphonomethyl)(1,1'-biphenyl)-3-propanoic acid
• Dizocilpine Maleate
• Haloperidol

Topics

• Animals
• Antipsychotic Agents (antagonists & inhibitors)
• Binding, Competitive
• Biphenyl Compounds (chemistry, pharmacology)
• Catalepsy (chemically induced, drug therapy)
• Dizocilpine Maleate (chemistry, pharmacology)
• Excitatory Amino Acid Antagonists (chemistry, pharmacology)
• Haloperidol (antagonists & inhibitors)
• Male
• Molecular Structure
• Neuroprotective Agents (chemistry, pharmacology)
• Propionates (chemistry, pharmacology)
• Rats
• Rats, Sprague-Dawley
• Receptors, N-Methyl-D-Aspartate (antagonists & inhibitors)
• Statistics, Nonparametric
• Structure-Activity Relationship