HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

The behavioural effects of MK-801: a comparison with antagonists acting non-competitively and competitively at the NMDA receptor.

Abstract
The selective non-competitive NMDA receptor antagonist, MK-801, potently blocked convulsions induced in the mouse by N-methyl-DL-aspartic acid (NMDLA) with an i.v. ED50 dose of 0.2 mg/kg. Similar doses of MK-801 were also effective in blocking seizures induced by pentylenetetrazol (PTZ), electroshock and by sound in audiogenic seizure-prone animals. Other less selective non-competitive NMDA receptor antagonists including phencyclidine (PCP), thienylcyclohexylpiperidine (TCP), (+)-N-allylnormetazocine [+)-NANM, (+)-SKF 10,047) and ketamine also blocked NMDLA-induced seizures with a rank order of potency of MK-801 greater than PCP greater than TCP = (+)-NANM greater than ketamine. The competitive NMDA receptor antagonist, 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) blocked NMDLA-induced seizures with an ED50 of 4.5 mg/kg, 22- and 560-fold more potently than the competitive antagonists, 2-DL-amino-7-phosphonoheptanoic acid (2-APH) and 2-DL-amino-5-phosphonovaleric acid (2-APV), respectively. MK-801 was the most potent of the non-competitive antagonists to induce a motor syndrome including head weaving, body rolling, increased locomotion and ataxia, characteristic of the behavioural response to PCP in the mouse. The syndrome was also present following injection of the competitive NMDA receptor antagonists, although they were generally less potent (probably a reflection of poor brain penetration) and less efficacious than the non-competitive antagonists. For all compounds except CPP, the anticonvulsant ED50 dose was close to the minimum effective dose to induce motor stimulation: CPP was 5- to 10-fold more potent as an anticonvulsant.(ABSTRACT TRUNCATED AT 250 WORDS)
AuthorsM D Tricklebank, L Singh, R J Oles, C Preston, S D Iversen
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 167 Issue 1 Pg. 127-35 (Aug 11 1989) ISSN: 0014-2999 [Print] Netherlands
PMID2550253 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anticonvulsants
  • Dibenzocycloheptenes
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Neurotransmitter
  • Aspartic Acid
  • N-Methylaspartate
  • Ketamine
  • Dizocilpine Maleate
  • SK&F 10047
  • tenocyclidine
  • Phenazocine
  • Phencyclidine
Topics
  • Animals
  • Anticonvulsants (pharmacology)
  • Aspartic Acid (analogs & derivatives, pharmacology)
  • Behavior, Animal (drug effects)
  • Binding, Competitive
  • Dibenzocycloheptenes (pharmacology)
  • Discrimination Learning (drug effects)
  • Dizocilpine Maleate
  • Dose-Response Relationship, Drug
  • Ketamine (pharmacology)
  • Male
  • Motor Activity (drug effects)
  • N-Methylaspartate
  • Phenazocine (analogs & derivatives, pharmacology)
  • Phencyclidine (analogs & derivatives, pharmacology)
  • Rats
  • Rats, Inbred Strains
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Neurotransmitter (antagonists & inhibitors, metabolism)
  • Seizures (chemically induced)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: