1. Differential behavioral syndrome evoked in the rats after multiple doses of SSRI ﬂuoxetine with selective MAO inhibitors rasagiline or selegiline
Z. Speiser, T. Fine, L. Litinetsky, S. Eliash, E. Blaugrund, S. Cohen. J Neural Transm (2008) 115: 107–116
Rasagiline mesylate (batch 255400100), selegiline HCl (batch 251700298) and ﬂuoxetine HCl (batch 252101102) were obtained from Teva Pharmaceutical Industries Ltd (Netanya, Israel). All doses refer to base equivalents of the corresponding salts. Rasagiline and selegiline salts were dissolved in the rats’ drinking water at a concentration adjusted to deliver the required cumulative daily dose. The normal daily intake of water per rat is about 30mL. Thus, a rat weighing 250 g, at a dose of 0.1mg/kg/day, received daily 0.025mg rasagiline in 30mL water. In this case, the concentration of rasagiline was 0.0833mg=100mL. Concentrations to deliver higher doses were derived accordingly. Daily water intake was checked every second day. Fluoxetine HCl was dissolved in distilled water and injected i.p. in a volume of 2mL adjusted to deliver 10 mg/kg/day.
2. Protection Against Parkinson’s Disease Progression: Clinical Experience
Peter A. LeWitt* and Danette C. Taylor*. The Journal of the American Society for Experimental NeuroTherapeutics. Vol. 5, 210–225
The TEMPO trial (Rasagiline Mesylate [TVP-1012] in Early Monotherapy for Parkinson’s Disease Outpatients) was conducted in 404 early, untreated PD patients for 26 weeks as a randomized, double-blind, placebo- controlled clinical trial using rasagiline at doses of 1 and 2 mg/day. The primary efﬁcacy measure was the net change in total UPDRS score from baseline to 6 months; a secondary endpoint, similar to that of the DATATOP study, was the need for starting levodopa because of advancing disability. A novel feature of this study was its delayed-start design, used in an effort to differentiate the symptomatic effects of MAO-B inhibition from its possible neuroprotective actions. This differentiation was determined in the second 26-week phase of the study, in which the group initially receiving placebo was switched to rasagiline, 2 mg/day.
3. Theoretical investigation of the Anti-Parkinson drug rasagiline and its salts: conformations and infrared spectra
U.Ceren Başköse, Sevgi Haman Bayarı, Semran Sağlam, Hacı Özışık. Cent. Eur. J. Chem. • 10(2) • 2012 • 395-406
Molecular conformation plays a crucial role in the function and selectivity of flexible molecules of biological interest. It has been reported that solid rasagiline free base, rasagiline mesylate, and rasagiline ethanedisulfanate have no known polymorphs. Rasagiline possesses an indane ring, an -NH group, and a propargyl chain (Fig. 1). Indane and its derivatives are components of many biological molecules. It is composed of a benzene ring fused with a saturated five-membered ring. The substitution of the five-membered ring of indane gives rise to several conformers. The structure-activity relationship among rasagiline-related compounds suggests the crucial role of the propargyl moiety in these molecules.