Interactions of the beta carboline abecarnil with the high pressure neurological syndrome in a primate model.
The neurophysiological interactions between the high pressure neurological syndrome (HPNS) and a new beta carboline, abecarnil, were studied in the non-human primate Papio anubis. Abecarnil is a partial agonist at the benzodiazepine site on the GABA/benzodiazepine receptor. Six animals were exposed on two occasions to pressures of 91 ATA in an environment of helium and oxygen. One exposure was pretreated with a total dose of abecarnil 1.0 mg/kg, the other with an equivalent volume of vehicle. Treatment with abecarnil prevented the severe signs of HPNS occurring between 51 and 91 ATA. Onset pressures of the various signs were unaffected. Some signs, e.g. myoclonus, became more frequent when abecarnil was used. A residual protective effect of abecarnil was present 4 weeks after the dose was given, active at pressures less than 71 ATA. Changes with pressure in the EEG were recorded primarily from the frontal cortex, but were also present in the parietal and occipital areas of the left cortex. Amplitude and frequency spectra were calculated and changes with pressure in the four conventional wavebands, plus two others, analysed. The most striking change was the prevention by abecarnil of the pressure-induced 100% increase in alpha wave amplitude in the frontal region. It is concluded that modulation of GABA transmission is important in controlling the expression of HPNS.
Pearce
P C
PC
Anaesthesia/HPNS Research Group, Clinical Research Centre, Harrow, Middlesex, UK.
Halsey
M J
MJ
MacLean
C J
CJ
Passingham
S
S
Pearson
J
J
Mehta
R L
RL
Meldrum
B S
BS
Jordan
C J
CJ
Ward
E M
EM
D000818:Animals; D014151:Anti-Anxiety Agents / Q000097:blood / Q000627:therapeutic use*; D001274:Atmospheric Pressure; D001522:Behavior, Animal / Q000187:drug effects; D002243:Carbolines / Q000097:blood / Q000627:therapeutic use*; D004569:Electroencephalography / Q000187:drug effects; D005260:Female; D006371:Helium; D006610:High Pressure Neurological Syndrome / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D008297:Male; D009207:Myoclonus / Q000503:physiopathology / Q000517:prevention & control; D010100:Oxygen; D010215:Papio; D014202:Tremor / Q000503:physiopathology / Q000517:prevention & control; D014839:Vomiting / Q000503:physiopathology / Q000517:prevention & control
D014151:Anti-Anxiety Agents; D002243:Carbolines; D006371:Helium; C062769:abecarnil; D010100:Oxygen