A new formulation of selegiline: improved bioavailability and selectivity for MAO-B inhibition

  title={A new formulation of selegiline: improved bioavailability and selectivity for MAO-B inhibition},
  author={Anthony Clarke and Francesca Mary Brewer and E. Stewart Johnson and N. Mallard and Florian Hartig and S. Taylor and T. H. Corn},
  journal={Journal of Neural Transmission},
Summary. 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… 
A new low-dose formulation of selegiline: clinical efficacy, patient preference and selectivity for MAO-B inhibition
Summary. Three studies were performed using a fast dissolving formulation of selegiline hydrochloride designed for buccal absorption “Zydis Selegiline”. The aim of the first study was to compare the
Evidence that Formulations of the Selective MAO-B Inhibitor, Selegiline, which Bypass First-Pass Metabolism, also Inhibit MAO-A in the Human Brain
The results provide the first direct evidence of brain MAO-A inhibition in humans by formulations of selegiline, which are currently postulated but not verified to target brain MAo-A in addition toMAO-B.
Transdermal Selegiline: The New Generation of Monoamine Oxidase Inhibitors
Clinicians should familiarize themselves with the properties and indications for the new generation of MAOIs and it is possible that STS may demonstrate benefit in MDD with atypical features or MDD resistant to other antidepressants.
A Sensitive HPLC-MS/MS Method for the Quantification of Selegiline in Beagle Dog Plasma: Application to a Pharmacokinetic Study
To develop a reliable and sensitive high-performance liquid chromatographytandem mass spectrometry (HPLC-MS/MS) method for the quantification of selegiline in Beagle dog plasma and apply the
Pharmacokinetics of selegiline, R-methamphetamine, R-amphetamine, and desmethylselegiline in oral fluid after a single oral administration of selegiline.
There is a period of time in OF in which only MA and AM are present without SG and DM-SG after a single dose of SG, which could provide supplementary interpretation for OF tests in forensic science and drug treatment programs.
Selegiline: a molecule with innovative potential
Cell and molecular studies revealed interesting properties of selegiline opening new possibilities for neuroprotective mechanisms and a disease-modifying effect of MAO-B inhibitors.
A novel formulation of selegiline for the treatment of Parkinson’s disease
These studies clearly demonstrated that selegiline was safe and significantly improved “on” time in PD patients experiencing end-of-dose “wearing off,” thus negating some of the levodopa-potentiating effects of the drug.
The pharmacokinetic evaluation of selegiline ODT for the treatment of Parkinson's disease
The only well-justified advantage of the ODT formulation is its convenient use in parkinsonian patients who have difficulties in swallowing the regular formulation, and it suggests that the metabolites do not participate significantly in the therapeutic or toxic effects of selegiline.
Monamine Oxidase Inhibitors: Current and Emerging Agents for Parkinson Disease
A randomized clinical trial is underway to confirm preclinical and preliminary clinical data suggesting rasagiline has disease-modifying effects, and a new formulation of seLegiline (Zydis selegiline) has been evaluated in 2 small, placebo-controlled studies as adjunctive therapy to levodopa.
Novel Spectrophotometric Methods for the Determination of Selegiline Hydrochloride in Bulk and Its Pharmaceutical Preparation
The results obtained indicate that the methods are free from interference of the ingredients; thus they are successfully applied to pharmaceutical formulations.


Clinical Pharmacokinetics and Pharmacodynamics of Selegiline
  • I. Mahmood
  • Biology, Medicine
    Clinical pharmacokinetics
  • 1997
Transdermal administration of seLegiline resulted in an increase in the plasma concentrations of selegiline and a decrease in the formation of its metabolites, indicating that the extensive first-pass effect is avoided when selegILine is given transdermally.
The influence of metabolism on the MAO-B inhibitory potency of selegiline.
It is suggested, that (-)-deprenyl is metabolised mainly in the liver by microsomal cytochrome P-450 dependent mono-oxygenases, and it has an intensive first-pass metabolism.
Rasagiline [N‐propargyl‐1R(+)‐aminoindan], a selective and potent inhibitor of mitochondrial monoamine oxidase B
Data indicate that this inhibitor like selegiline may be a useful agent in the treatment of Parkinson's disease in either symptomatic or L‐DOPA adjunct therapy, but lack of amphetamine‐like metabolites could present a therapeutic advantage for rasagiline.
Deprenyl (selegiline), a selective MAO-B inhibitor with active metabolites; effects on locomotor activity, dopaminergic neurotransmission and firing rate of nigral dopamine neurons.
The data suggest that the stimulatory effect on locomotor activity and dopamine synthesis is not related to a monoamine oxidase-B blocking action of the drug or to a putative effect on DA reuptake, but rather to effects of metabolites of thedrug (e.g., l-methamphetamine).
The molecular pharmacology of L-deprenyl.
R-(-)-deprenyl (Selegiline, Movergan) facilitates the activity of the nigrostriatal dopaminergic neuron.
  • J. Knoll
  • Biology, Chemistry
    Journal of neural transmission. Supplementum
  • 1987
(-)Deprenyl, when administered continuously in small doses (0.25 mg/kg/day), facilitates the activity of the nigrostriatal dopaminergic neuron because of its highly characteristic complex spectrum of
Slow recovery of human brain MAO B after L‐Deprenyl (Selegeline) withdrawal
The slow turnover of brain MAO B suggests that the current clinical dose of L‐deprenyl may be excessive and that the clinical efficacy of reduced dosing should be evaluated, and the first measurement of the synthesis rate of a specific protein in the living human brain is measured.
Effect of Long‐Term Treatment with Selective Monoamine Oxidase A and B Inhibitors on Dopamine Release from Rat Striatum In Vivo
DA metabolism was reduced only by clorgyline, whereas neuronal release of DA was enhanced by both MAO‐A andMAO‐B inhibitors on chronic administration, and the enhanced DA release does not appear to be dependent on production of amphetamine‐like metabolites of the inhibitor.
Monoamine Oxidase Activity and Monoamine Metabolism in Brains of Parkinsonian Patients Treated with l‐Deprenyl
The data indicate that the therapeutic actions of l‐deprenyl may lie in its selective inhibition of MAO‐B resulting in increased brain levels of DA formed from L‐dihydroxyphenylacetic acid (L‐DOPA).
CYP2B6 and CYP2C19 as the major enzymes responsible for the metabolism of selegiline, a drug used in the treatment of Parkinson's disease, as revealed from experiments with recombinant enzymes.
The data strongly indicate that the high extent of interindividual variation seen in vivo for selegiline clearance is caused by the metabolism of the compound by the highly polymorphic CYP2B6 and CYP 2C19.