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.Riluzole is an inhibitor of glutamate release and anon-competitive antagonist at N-methyl-D-aspartate (NMDA) receptors.It is known that theH reflex and flexor reflexes in experimental animals are mediated by different subtypes ofionotropic glutamate receptors; the flexor reflex by NMDA receptors and the H reflex bynon-NMDA receptors.Therefore, spinal reflexes may provide an opportunity to investigateglutamatergic neurotransmission in humans in vivo.The authors investigated wetherriluzole differentially alters the H reflex and flexor reflexes in patients with ALStreated with the drug.15 controls and 10 patients with ALS, at onset and after3 months oftreatment with 50 mg riluzole BID, participated to the study which was approved by theethic commission of the Humboldt University.The mean latency for the H reflex wasunchanged inpatients with ALS before and after treatment with riluzole: 31.0 (SD 3.3) msand 30.4 (SD 3.0) ms.The respeetive values for the flexor reflexes were 72.5 (SD 6.6) msat onset and 121.1 (SD 17.6) ms (P<0.05) after 3 months of treatment with riluzole.Theresults observed show that the H reflex and the flexor reflex are differentially affectedin patients with ALS treated with riluzole :the latency of the I-I reflex did not change,whereas the latency of the flexor reflex increased.These results are consistent with theknown pharmacological properties of riluzole These diagnostic tests can be used toevaluate pharmacological therapies with glutamate antagonists.142 - RILU0285Vogels OJM; Oyen W; Van Engelen BGM; Padberg GWAM; Horstink MWIMPostsynaptic striatal dopaminergic deficit in sporadic amyotrophic lateral sclerosis andits possible amelioration by riluzole (ENG)J NEUROL, (1997) 244 (6 SUPPL 3) S16 AB: 467TH MEETING OF THE EUROPEAN NEUROLOGICAL SOCIETY, RHODES, GREECE, 14-18/06/97Neuropathological, positron emission tomography and single-photon emission computedtomography (SPECT) investigations have indicated an involvement of the presynapticdopaminergic system in amyotrophic lateral sclerosis (ALS).Purpose of this study is toinvestigate whether (subclinical) dopaminergic deficit in ALS also occurs at the striatalpostsynaptic D2-receptor level and whether this deficit, if present, can be reserved bythe glutamate antagonist riluzole.Five patients with definitive ALS (E1 Escorialcriteria) and five age-matched control subjects underwent (123I) IBZM-SPECT to quantitatepostsynaptic D2-receptor binding During riluzole treatment two ALS patients underwent asecond (1231) IHZM-SPECT.Statistical analysis was performed with the Mann-Whitney U-test(five ALS patients versus five age-matched controls) and with the Wilcoxon test formatched pairs (two ALS patients before and during riluzole treatment).All five definiteALS patients showed slight to severe postsynaptic D2-receptor loss in both left (p =0.009) and right hemispheres (p = 0.009).Riluzole improved postsynaptic D2-receptor lossin all tour hemispheres to subnormal levels (p= 0.068).In ALS, the lower availability ofD2-receptors on striatal cells may be caused by cell loss.However, the increasedavailability of straital D2-receptors during riluzole therapy suggests receptor downregulation, rather than merely cell loss More ALS patients are currently underinvestigation to await further confirmation of these preliminary results.143 - RILU0252Hoffman U; Quasthoff S; Kuhn M;Hakk K; Franke C; Schrank B; Ochs G; Reiners K; Giess R;Bostock H; Grafe PThreshold electrotonus measurements in the diagnosis and follow up of ALS patients (ENG)ELECTROENCEPHALOGR CLIN NEUROPHYSIOL, (1996) 99 (4) 348-349 AB: 83Threshold electrotonus tracking in ALS patients has revealed a specific axonal ion channeldysfunction in peripheral motor nerves (Bostok et al, Brain (1995) 117 225-234).The aimof the present study was to determine the sensitivity of the method in ALS and whether theobserved abnormalities would change during the progression of the disease with or withouttreatment with riluzole.Only 68% of 71 patients with a diagnosis of definite ALS who wereincluded in the study exhibited the previously described characteristics abnormalities.The abnormalities seen in these patients could not be correlated to ongoing fasciculationsor reduction in muscle compound potential amplitude.Furthermore, abnormalities could onlybe seen in patients with lower motoneuron signs, while patients which predominantly signsof a pathologic first motoneuron were normal.Under the treatment with riluzole 7 patientsout of 21 patients which exhibited the characteristic 'type I' abnormality became normalThis change in threshold electrotonus to normality was independent of the progression ofthe disease.In conclusion, threshold electrotonus tracking can provide helpfulinformation about the pathophysiology of ALS.However, the sensitivity of the method todetect ALS specific abnormalities in ALS patients is low.144 - RILU0168Saletu B; Grunberger J; Anderer P; Linzmayer LEffects of the novel neuroprotective agent, riluzole, on human brain function andbehavior: I.Double-blind, placebo-controlled EEG mapping and psychometric studies undernormoxia (ENG)METHODS FIND EXP CLIN PHARMACOL, (1996), 18 (1) 55-66, 49REFIn a double-blind, placebo-controlled, crossover study, the encephalotropic andpsychotropic properties of single oral doses of the novel neuroprotective agent, riluzole,were investigated utilizing EEG mapping and psychometry.Twenty healthy young volunteersreceived randomly at weekly intervals, placebo, 50, loo and 200 mg riluzole
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