1.The effect of R-(-)-deprenyl administration on reproductive parameters of rat males.
Mihalik J1, Mašlanková J2, Solár P3, Horváthová F1, Hubková B2, Almášiová V4, Šoltés J5, Švaňa M5, Rybárová S1, Hodorová I6. Eur J Pharmacol. 2015 May 5;754:148-52. doi: 10.1016/j.ejphar.2015.02.030. Epub 2015 Feb 26.
The aim of the study was to investigate the effect of R-(-)-deprenyl administration on the reproductive parameters of rat males. After 30 days of intraperitoneal administration of saline or 0.0025mg/kg (10(-5)mol/l) of R-(-)-deprenyl dissolved in saline, males were mated with females of the same strain. Subsequently, animals were killed by thiopental, and their blood and sperm were collected. We found that epididymis of males exposed to R-(-)-deprenyl had higher sperm count (P<0.05), and females who mated with these males gave birth to a greater number of offspring (P<0.05) compared to control. The blood of experimental animals contained higher levels of testosterone (P<0.05), FSH (P<0.01), and total antioxidants (P<0.01). We did not detect sperm DNA fragmentation in control or in experimental males. Interestingly, round spermatids were often observed inside seminiferous tubules of experimental animals, but obviously without any negative consequences on male fertility.
2.In vitro antifungal activity of antipsychotic drugs and their combinations with conventional antifungals against Scedosporium and Pseudallescheria isolates.
Homa M1, Galgóczy L2, Tóth E1, Tóth L1, Papp T3, Chandrasekaran M3, Kadaikunnan S3, Alharbi NS3, Vágvölgyi C4. Med Mycol. 2015 Nov;53(8):890-5. doi: 10.1093/mmy/myv064. Epub 2015 Aug 26.
In the present study, in vitro antifungal activities of five antipsychotic drugs (i.e., chlorpromazine hydrochloride, CPZ; trifluoperazine hydrochloride, TPZ; amantadine hydrochloride; R-(-)-deprenyl hydrochloride, and valproic acid sodium salt) and five conventional antifungal drugs (i.e., amphotericin B, AMB; caspofungin, CSP; itraconazole; terbinafine, TRB and voriconazole, VRC) were investigated in broth microdilution tests against four clinical and five environmental Scedosporium and Pseudallescheria isolates. When used alone, phenothiazines CPZ and TPZ exerted remarkable antifungal effects. Thus, their in vitro combinations with AMB, CSP, VRC, and TRB were also examined against the clinical isolates. In combination with antifungal agents, CPZ was able to act synergistically with AMB and TRB in cases of one and two isolates, respectively. In all other cases, indifferent interactions were revealed. Antagonism was not observed between the tested agents.
3.Metabolic transformation plays a primary role in the psychostimulant-like discriminative-stimulus effects of selegiline [(R)-(-)-deprenyl].
Yasar S1, Justinova Z, Lee SH, Stefanski R, Goldberg SR, Tanda G. J Pharmacol Exp Ther. 2006 Apr;317(1):387-94. Epub 2005 Dec 13.
l-Deprenyl [selegiline, (R)-(-)-deprenyl] is a selective inhibitor of monoamine oxidase B (MAO-B) used in the treatment of Parkinson's disease and proposed as an antidepressant and an aid for cigarette-smoking cessation and treatment of psychostimulant abuse. Beneficial therapeutic effects of (R)-(-)-deprenyl may also result from indirect actions. Brain levels of dopamine and beta-phenylethylamine (beta-PEA), a behaviorally active endogenous trace amine, increase after (R)-(-)-deprenyl treatment due to MAO-B blockade and (R)-(-)-deprenyl is metabolized to (R)-(-)-methamphetamine and (R)-(-)-amphetamine, suggesting that (R)-(-)-deprenyl may have psychostimulant-like behavioral effects. Indeed, (R)-(-)-deprenyl produces psychostimulant-like discriminative-stimulus effects in experimental animals. Here, we tested the hypothesis that psychostimulant-like behavioral effects of (R)-(-)-deprenyl are mainly mediated by its metabolites. Male Fisher F344 rats were trained to discriminate i.
4.A new formulation of selegiline: improved bioavailability and selectivity for MAO-B inhibition.
Clarke A1, Brewer F, Johnson ES, Mallard N, Hartig F, Taylor S, Corn TH. J Neural Transm (Vienna). 2003 Nov;110(11):1241-55.
Seven randomised comparative studies were conducted in healthy volunteers to compare the pharmacokinetic and pharmacodynamic profiles of selegiline hydrochloride in a new formulation designed for buccal absorption "Zydis Selegiline" (1.25-10 mg) with conventional selegiline hydrochloride tablets "conventional selegiline tablets" (10 mg). A total of 156 healthy volunteers participated in these studies. Plasma concentrations of selegiline and its primary metabolites, N-desmethylselegiline (DMS), l-amphetamine (AMT), and l-methamphetamine (MET) were measured using Gas Chromatography Mass Spectrometry (GCMS) and gas liquid chromatography (GLC) assays. Inhibition of monoamine-oxidase type B (MAO-B) and monoamine oxidase type A (MAO-A) activity was determined by measurement of as beta-phenylethylamine (PEA) by GCMS and 5-hydroxyindoleacetic acid (5-HIAA) by High Performance Liquid Chromatography (HPLC) assays. Almost a third (2.96 mg) of a 10 mg selegiline dose in Zydis Selegiline was absorbed pre-gastrically (predominantly buccally) within 1 minute.