The effect of various drug pretreatments on the convulsions and cerebellar cyclic nucleotide changes induced by the convulsant 4-isopropyl-2,6,7-trioxa-1-phosphatbicyclo(2,2,2)octane-1-oxide(IPTBO).
The effects of pretreatment of mice with some drugs which modify GABAergic neurotransmission on the convulsions and cerebellar cyclic nucelotide level changes induced by the subsequent intracerebroventricular administration of 4-isopropyl-2,6,7-trioxa-1-phosphabicyclo(2,2,2)octane-1-oxide (IPTBO) have been studied. Muscimol, pentobarbitone and diazepam reduced the number of animals convulsing and prolonged the time to onset of convulsions in those animals which did, whereas baclofen and ?-acetylenic GABA had no effect on the number of animals convulsing but did prolong seizure latency. All the drugs except baclofen prevented the increase in cyclic GMP concentrations following IPTBO treatment. Pentobarbitone, baclofen and ?-acetylenic GABA caused significant increases in the concentrations of cyclic AMP, whereas there was no marked effect of treatment with IPTBO alone on the levels of this nucleotide: however, IPTBO reduced the extent of the increases produced by the drugs. The results are discussed in the context of the mechanism of action of IPTBO and the involvement of GABAergic neurotransmission in convulsant and anticonvulsant activities.
Blenkinsop
I S
IS
Chemical Defence Establishment, Porton Down, Salisbury, Wiltshire, England.
Coult
D B
DB
Davies
W E
WE
Howells
D J
DJ