Electropharmacograms of rasagiline, its metabolite aminoindan and selegiline in the freely moving rat.
BACKGROUND
Rasagiline and selegiline are classified as monoamine oxidase B (MAO-B) inhibitors. The present investigation deals with time-dependent electrical frequency changes (electropharmacograms) induced by these, as well as by aminoindan, the major metabolite of rasagiline.


METHODS
Adult rats (day-night converted, >5 months old) were fitted with 4 bipolar concentric steel electrodes connected to a small base plate, which was positioned stereotactically for insertion of the electrodes into the frontal cortex, hippocampus, striatum and reticular formation. The plate carried a small plug to receive a telemetric device during the experimental session. Changes in field potentials were recorded during a pre-drug reference period of 45 min, followed by intraperitoneal administration and 5 h of recording thereafter. Data were transmitted wirelessly for frequency analysis. Data from 10 animals treated within a crossover design were averaged.


RESULTS
A dose of 0.25 mg/kg i.p. rasagiline produced statistically significant decreases in spectral alpha2 and beta1 power. Higher dosages showed a linear enhancement of this effect. A similar pattern was obtained after administration of aminoindan (2-10 mg/kg), but of shorter duration. Selegiline produced a similar pattern only for the first 1-2 h. After this, statistically significant increases in delta and theta power were observed.


CONCLUSIONS
Despite the feature of MAO-B inhibition in both drugs and its reflection in the initial changes of the frequency pattern during the first hour, the pharmacological action of selegiline during the following hours differs profoundly from that of rasagiline, presumably due to the toxicity of its major metabolites methamphetamine and amphetamine.
Dimpfel
Wilfried
W
Justus Liebig University Giessen, Sportparkstrasse 9, Wetzlar, Germany. w.dimpfel@neurocode-ag.com
Hoffmann
Josef A
JA
D000818:Animals; D058256:Brain Waves / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007189:Indans / Q000494:pharmacology*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D012642:Selegiline / Q000494:pharmacology*
D007189:Indans; D008996:Monoamine Oxidase Inhibitors; C031967:rasagiline; D012642:Selegiline; C016992:1-aminoindan