Lack of effect of lamotrigine against HPNS in rodent and primate models

Abstract

The neurophysiological effects of the novel anticonvulsant lamotrigine on the high pressure neurological syndrome, HPNS, were investigated in the rat and nonhuman primate Papio anubis. Rats were exposed to pressure at a rate of 3 ATA per min in a helium/oxygen environment. They were pretreated with either lamotrigine isethionate 15, 30, or 60 mg/kg IP or control vehicle. After 15 and 30 mg/kg there were no changes in onset pressures for any of the grades of tremor or myoclonus. After 60 mg/kg, tremor was much slower, at 7–9 Hz, than the 15–20 Hz seen in controls. Four baboons were exposed to pressure at 0.33 ATA per min in the same environment and treated with lamotrigine isethionate at 7.5 mg/kg/h IV. Each animal underwent a control and a drug-treated exposure. No changes in the onset or severity of HPNS behavioural signs were observed. However, an increase in alpha wave amplitude of the EEG was almost prevented. In both species sustained myoclonic jerking occurred at pressures similar to those at which seizure activity was observed in control exposure. It is concluded that although lamotrigine is protective in several models of neuronal excitation, it is ineffective in protecting againsts behavioural signs associated with high atmospheric pressure.