Activation of group III metabotropic glutamate receptors in selected regions of the basal ganglia alleviates akinesia in the reserpine-treated rat.

1. This study examined whether group III metabotropic glutamate (mGlu) receptor agonists injected into the globus pallidus (GP), substantia nigra pars reticulata (SNr) or intracerebroventricularly (i.c.v.) could reverse reserpine-induced akinesia in the rat. 2. Male Sprague-Dawley rats, cannulated above the GP, SNr or third ventricle, were rendered akinetic with reserpine (5 mg kg(-1) s.c.). 18 h later, behavioural effects of the group III mGlu receptor agonists L-serine-O-phosphate (L-SOP) or L-(+)-2-amino-4-phosphonobutyric acid (L-AP4) were examined. 3. In reserpine-treated rats, unilateral injection of L-SOP (2000 and 2500 nmol in 2.5 microl) into the GP produced a significant increase in net contraversive rotations compared to vehicle, reaching a maximum of 83+/-21 rotations 120 min(-1) (n=8). Pretreatment with the group III mGlu receptor antagonist methyl-serine-O-phosphate (M-SOP; 250 nmol in 2.5 microl) inhibited the response to L-SOP (2000 nmol) by 77%. Unilateral injection of L-SOP (250-1000 nmol in 2.5 microl) into the SNr of reserpine-treated rats produced a dose-dependent increase in net contraversive rotations, reaching a maximum of 47+/-6 rotations 30 min(-1) (n=6). M-SOP (50 nmol in 2.5 microl) inhibited the response to L-SOP (500 nmol) by 78%. 4. Following i.c.v. injection, L-SOP (2000-2500 nmol in 2.5 microl) or L-AP4 (0.5-100 nmol in 2 microl) produced a dose-dependent reversal of akinesia, attaining a maximum of 45+/-17 (n=8) and 72+/-3 (n=9) arbitrary locomotor units 30 min(-1), respectively. 6. These studies indicate that injection of group III mGlu receptor agonists into the GP, SNr or cerebral ventricles reverses reserpine-induced akinesia, the mechanism for which remains to be established.

Pharmacokinetic study of the relative bioavailability and bioequivalence after oral intensive or repeated short term treatment with two polyamino acid formulations.

The authors studied the relative bioequivalence and bioavailability of two oral polyamino-acid formulations (packet and flacon), based on 4 amino acids (L-glutamine, L-phosphoserine, L-phosphothreonine and L-arginine) in association with vitamin B12 (Bio-logos, Sigma Tau Pharma S.A). Open-trial testing was carried out after intensive treatment and on the attainment of sustained levels. 50 healthy volunteers (27 males, 23 females), ranging in age from 23 to 32 years, were included in the study. The pharmacokinetic behaviour of the various active ingredients was examined at a haematic level. Possible undesirable side-effects, resulting from treatment, were also examined during the study. The mean pharmacokinetic constants considered (Ke1, Cmax and t1/2) generated an almost overlapping AUC (area under the curves) for all homologous components contained in both pharmaceutical forms. This indicates almost complete bioequivalence. The mean index for the rate of relative bioavailability was, in fact, estimated to be 106.3 +/- 12.4%. Repeated treatment did not appear to disturb the absorption mechanisms of the active ingredients contained in either of the two formulations examined, maintaining the relative bioavailability relationship within a negligible range, with a statistically non-significant difference (Student's t test for coupled data). A few episodes, characterized by slight increases in excitability, were reported for both preparations in two patients (4%).