ABSTRACTS 695

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com’AEATI”E NEUROLOGICAL AND ANTICONVuLSANT EFFECTS OF

BAcLOFEN (BF), MUSCIMOL (MC), DUZEPAM (02) AND Y-BUNRO- I&TONE 0%). P. S. Bernard, R. Sobiski and K. Da'aoo. Res. Dept., Pharmaceuticals Div., CIBA-GEIGY Corp., Summit, N.J. 07901

SF, MC, DZ and GEL differed widely in rheir anficonVul- *eat accivitv in classical aainial te*te.. DZ f< 10 i-P.) prevented &razol-, picrofoxin- and eleecroshoek-induced sei=urea; NC (< I. 1.p.) prevented uetrazol- and ~icrotoxin- but not elecrroshoek-induced seizutaa; GBL (64 i.p.) I%*- vented picrotoxin- but not meLrmol- or electroshock-induced seizures; and BF (20 i.p.) vss inactive in.all the above procedures.

BY reduces the release of Slutmic acid in vitro (Potashncr. Cansd. J. Physiol. Pbetm. 56:150, 1978). Keinic acid (VA) is a cytoroxic convulsant which requires an in- tact glutaminergic neuron syvtem to Cam% some of its cyto- tonic and, presumably, neurological changss. whrn KA (10 t.v.) was administered to rats e neurological syndrome ~121s produced consisring of wet-dog shakes, hypers*li"ation, hindlimb oc~stching and clonic seizures. BF (IO-20 i.p.), DZ (3-10 i.P.), MC (0.3-l i.p.) and GEL (30-300 i.p.) stLe"- uated KA-induced hypersalivatim, cl.onic seizures and hind- limb scratching. DZ and UC, but not SF or CBL also reduced the incidence of vet dog shakeu.

These rcaulcs extend the antic0nvu1.anc Profile Of DZ,

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INTERACTIONS ANONG WCLEO'I'IDES. INORGANIC PEOSPSATE ANO PYPIOGXAL-pHOSpZ,ATE IN TIlE REGGLAITON OF BRAIN GLCTARATE D~~~~S. I).L. Maarcin. l&P. Weeley, S.B. Next%,, loa S. Pedarsm. Depf. of ChCIDietsy‘, Univ. of xd.. College Park, naryland 20742.

The regulatory properties of brain GAD have been studied with rat-brain supernatanta aaP parLially purified CAD from hog brain. GAD is strongly inhibited by AIT and othsr nu- cleotidea. Ihis inhibition is relieved by pyridoral-F end

pi. About 80% of CAD is in the holoonryme form after ex- haustive dialysis i"dicaCi"B that, Pyridoxal-p is tightly bound Co the enzyae. However, Slummate promotes dlsaocia- tion of pyridoxal-P sugBestir& chat there Ls conrinuoua for- mation of apoenryme *a. Incubecien of *p&AU (prepared froa ho$ or rat brain or obtaiard from vitamin &j deficient rats) with pyridoxal-P resulted fn a slow reactivario,,. Addition of l-10 mH pi greatly increesed the rate of ectiva- tion. APO- end holoGAn eluted from Sephedex G-200 in e,.mmost identical volmes indicating chat interconversion of apo- end haloGAD did “ot involve submit dissociation. A’,T strongly inhibits exhaustively dialyzed hog-brain GAD in the absence of Pyridoxal P. Since CAI cannot be activated in the absence of pyridoxel p, this result svggesta that AT? does not inhibit by blocking r~~~tl"oxIo.. The present evi- dence sugSesta chat regulac<on of GAD involves a b&,ance of factors which coetr~l a cycle of inecrivation and remrim- tioll through fornation of apoen~yma (prowted by SlueaaPte) and its reectivation by pyridoxrrl-P (pronoted by Pi). Ubether ATP interacts with thie cycle is under study.

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A study nf the GARA recepto: .&sing 'H-Ino~vncinc, J.P. Collins. 38ne A. MEDOnald md R.P. Ilcvton, Deprrtment of Chemistry, City of Inndon Polytechnic 31 Jewy Stjeft, London EC3N 2EY. Rn&w,d and l Glaxo- Allenbury Lmrted, WRIT, "e&a., EnEland. Isoguvacine (1) her been shown to be 4 putoti MB9i agonist. We hwc studied the sodium independent binding characteristics of JH-Iso@vacine on the GABA receptor. Km-tritonised synaptosoml membranes vere prepared by the nethod of Ennb and Snyder. and we ham investigated the eSPects oi incubnting these nembr~es vith hi& specific activity %I-Isowvacine in the prerence ci various drums. Bindis Y&S sham to ix both saturable sad stereospecific. Ehrxirsl displlncenent URS schievcd uain([ fold isoSxmwinc and ves of the order of 50% of total counta bound. ED5Gs of Isoeuvacine, GABA, %mcinol. (+) B>cuculline netho- bromide were ?ound to be respectively: O.lyM. O.luH, O.OluM and O.luM. (-) Bicuculline methobromide was without efreet on the bindqng, Results vi11 be reported for other drugs studied. viz.: picrotoxinin. picrotin, t-butybi- cyclophosphatc, chlordiszepoxide, diszepan, and amino- propme nulphonic acid.