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Metaphit, an isothiocyanate analog of PCP, induces audiogenic seizures in mice
E A Debler1, M N Lipovac, A Lajtha
1Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, New York, NY 10035.
Abstract:
Metaphit induces audiogenic seizures in mice. The most severe clonic/tonic seizures occur 18-24 h after metaphit administration. After 48 h the incidence of the seizure episodes begin to diminish. These audiogenic seizures can be prevented by the administration of either PCP or MK-801 24 h after metaphit and 30 min prior to audio stimulation. These seizures may be due to a modulation of the PCP recognition site by metaphit which results in an enhanced probability that the NMDA/PCP ion channels are open.
Insights
Metaphit triggers audiogenic seizures in mice, peaking 18-24 hours post-administration. These seizures, linked to NMDA/PCP ion channel activity, can be prevented by PCP or MK-801.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Metaphit is known to induce seizures.
- The exact mechanism of metaphit-induced seizures requires further elucidation.
Purpose of the Study:
- To investigate the time course and potential mechanisms of metaphit-induced audiogenic seizures.
- To evaluate the efficacy of NMDA receptor antagonists in preventing these seizures.
Main Methods:
- Administration of metaphit to mice to induce audiogenic seizures.
- Assessment of seizure incidence and severity at various time points.
- Administration of phencyclidine (PCP) or MK-801 to assess their preventative effects.
Main Results:
- Metaphit induced audiogenic seizures in mice, with peak severity observed 18-24 hours post-administration.
- Seizure incidence decreased after 48 hours.
- Administration of PCP or MK-801 24 hours after metaphit and 30 minutes before audio stimulation prevented seizures.
Conclusions:
- Metaphit-induced audiogenic seizures are likely mediated by the modulation of the phencyclidine (PCP) recognition site.
- This modulation enhances the probability of N-methyl-D-aspartate (NMDA)/PCP ion channel opening, leading to seizures.
- NMDA receptor antagonists show potential in mitigating metaphit-induced seizure activity.
