Abstract | RATIONALE: OBJECTIVE: METHODS: Animals chronically treated with haloperidol for a period of 40 weeks exhibited significantly more vacuous chewing movements (VCMs), as compared to vehicle-treated controls. In a series of acute experiments, rats received: amantadine (10, 20, and 40 mg/kg i.p.), a low-affinity, uncompetitive NMDA-receptor antagonist (open channel blocker); dextrorphan (5, 10, and 20 mg/kg i.p.), an NMDA receptor channel antagonist; ifenprodil (2.5, 5, and 10 mg/kg i.p.), a noncompetitive allosteric NMDA receptor antagonist acting at the polyamine site; and Ro 25-6981 (2.5, 5, and 10 mg/kg i.p.), a potent and selective blocker of NMDA receptors which contain the NR2B subunit. RESULTS: All the drugs tested, except dextrorphan, reduced VCMs and tongue protrusions with varying efficacies and side effects profiles. Ro 25-6981 was found significantly more potent than amantadine and ifenprodil in reducing VCMs and tongue protrusions at all doses tested, and at the higher dose, it completely eliminated orofacial dyskinesia (p<0.05). CONCLUSIONS: These results suggest that NMDA receptors may play a significant role in the pathophysiology of tardive dyskinesia. Furthermore, antagonists showing selectivity for NMDA receptors containing the NR2B subunit may be particularly efficacious as novel therapeutic agents for the treatment of tardive dyskinesia and deserve further testing.
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Authors | Spiridon Konitsiotis, Christos Tsironis, Dimitrios N Kiortsis, Angelos Evangelou |
Journal | Psychopharmacology
(Psychopharmacology (Berl))
Vol. 185
Issue 3
Pg. 369-77
(Apr 2006)
ISSN: 0033-3158 [Print] Germany |
PMID | 16518645
(Publication Type: Journal Article)
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Chemical References |
- Antipsychotic Agents
- NR2B NMDA receptor
- Phenols
- Piperidines
- Receptors, N-Methyl-D-Aspartate
- Ro 25-6981
- Dextrorphan
- Amantadine
- Haloperidol
- ifenprodil
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Topics |
- Allosteric Regulation
- Amantadine
(therapeutic use)
- Animals
- Antipsychotic Agents
(adverse effects)
- Dextrorphan
(therapeutic use)
- Dose-Response Relationship, Drug
- Dyskinesia, Drug-Induced
(drug therapy, etiology)
- Haloperidol
(adverse effects)
- Male
- Phenols
(therapeutic use)
- Piperidines
(therapeutic use)
- Rats
- Rats, Wistar
- Receptors, N-Methyl-D-Aspartate
(antagonists & inhibitors)
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