Pc. Pearce et al., LACK OF EFFECT OF LAMOTRIGINE AGAINST HPNS IN RODENT AND PRIMATE MODELS, Pharmacology, biochemistry and behavior, 48(1), 1994, pp. 259-263
The neurophysiological effects of the novel anticonvulsant lamotrigine
on the high pressure neurological syndrome, HPNS, were investigated i
n the rat and nonhuman primate Papio anubis. Rats were exposed to pres
sure at a rate of 3 ATA per min in a helium/oxygen environment. They w
ere 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 6
0 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 exposur
e. 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 exposures. It is concluded that although lamotrigine is pro
tective in several models of neuronal excitation, it is ineffective in
protecting against behavioural signs associated with high atmospheric
pressure.