Metabolism of Selegiline [(-)-Deprenyl)]

Kalász, Huba; Magyar, K.; Szöke, Éva; Adeghate, Ernest; Adem, Abdu; Al‐Hasan, Muath; Nurulain, Syed M.; Tekes, Kornélia

doi:10.2174/0929867321666131218094352

Cited by 9 publications

(5 citation statements)

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“…Drugs also may be sources of formaldehyde. For example, Selegiline (Anipryl, L-deprenyl, Eldepryl, Emsam, Zelapar), which is used to treat Parkinson's disease, gives off formaldehyde as a byproduct as a result of the metabolic transformation circuit (219).…”

Section: Second Phase Of Methanol Catabolismmentioning

confidence: 99%

Metabolic Methanol: Molecular Pathways and Physiological Roles

Dorokhov

Shindyapina

Sheshukova

et al. 2015

Physiological Reviews

163

125

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Methanol has been historically considered an exogenous product that leads only to pathological changes in the human body when consumed. However, in normal, healthy individuals, methanol and its short-lived oxidized product, formaldehyde, are naturally occurring compounds whose functions and origins have received limited attention. There are several sources of human physiological methanol. Fruits, vegetables, and alcoholic beverages are likely the main sources of exogenous methanol in the healthy human body. Metabolic methanol may occur as a result of fermentation by gut bacteria and metabolic processes involving S-adenosyl methionine. Regardless of its source, low levels of methanol in the body are maintained by physiological and metabolic clearance mechanisms. Although human blood contains small amounts of methanol and formaldehyde, the content of these molecules increases sharply after receiving even methanol-free ethanol, indicating an endogenous source of the metabolic methanol present at low levels in the blood regulated by a cluster of genes. Recent studies of the pathogenesis of neurological disorders indicate metabolic formaldehyde as a putative causative agent. The detection of increased formaldehyde content in the blood of both neurological patients and the elderly indicates the important role of genetic and biochemical mechanisms of maintaining low levels of methanol and formaldehyde.

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Section: Second Phase Of Methanol Catabolismmentioning

confidence: 99%

Metabolic Methanol: Molecular Pathways and Physiological Roles

Dorokhov

Shindyapina

Sheshukova

et al. 2015

Physiological Reviews

163

125

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“…Contrary to selegiline and rasagiline, which show dyskinesia as a secondary effect in patients with advanced PD, safinamide has no methamphetamine metabolites (i.e. in contrast to selegiline) 34 and acts on the glutamatergic pathway (i.e. in contrast to rasagiline).…”

Section: Discussionmentioning

confidence: 92%

Emerging Role of Safinamide in Parkinson’s Disease Therapy

Kulisevsky¹

2015

European Neurological Review

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Parkinson’s disease is associated with motor complications, especially dyskinesias, which limit dopaminergic replacement therapy. Safinamide is a water-soluble, orally active a-aminoamide derivative that modulates dopaminergic and glutamatergic neurotransmission with a unique dual mechanism of action. It improves motor symptoms, motor complications, quality of life and ‘on’ and ‘off’ time even in combination with other Parkinson’s disease (PD) medications, such as dopamine agonists and levodopa (LD). Safinamide reduces ‘off’ time and extends ‘on’ time without troublesome dyskinesia. Furthermore, safinamide maintains its effects after long-term treatment and has a favourable pharmacokinetic and side-effect profile. It therefore has the potential to become an important drug in PD management. This review will summarise data from animals, healthy human subjects and patients with PD on the long-term efficacy and safety of safinamide.

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“…1 ) shows that the N-methyl group contains the source of radioactivity in the form of 14 C. However, the major metabolite of selegiline is methamphetamine which maintains the radioactivity keeping the 14 C-methyl group as well [27, 28]. …”

Section: Discussionmentioning

confidence: 99%

“…administration to avoid the first-pass effect of the drug. This method has been used and reported in our preliminary publications [9, 24, 25, 27]. However, to monitor the pharmacokinetics related to the use of selegiline in humans, oral administration should be applied.…”

Section: Discussionmentioning

confidence: 99%

Monitoring the Level of 14C-Labelled Selegiline Following Oral Administration

Kalász

Tekes

Faigl

et al. 2017

TOMCJ

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Background:Selegiline [(-)-deprenyl] is widely used for the treatment of Parkinson’s disease in humans.Objective:Time-dependence of tissue distribution of selegiline following per os administration to rats.Method:Oral administration of radiolabeled selegiline to rats resulted in a pattern of tissue distribution similar to that following intraperitoneal injection. Analyses were done using both reversed-phase HPLC and also by counting radioactivity in various body compartments of rats.Results:As a consequence of oral administration of 30 mg/kg of selegiline, its level in the stomach was extremely high (179.57 µg/g tissue through 54.67 µg/g at 15 min to 120 min), that is one magnitude higher than that in the serum level. High selegiline concentrations were also detected in the lacrimal glands (7.45 µg/g), kidneys (6.87 µg/g), livers (6.01 µg/g) and lungs (3.47 µg/g) after 30 minutes of application, which were higher than after intraperitoneal injections.Conclusion:The relatively high tissue levels remained for 120 min monitoring. Selegiline levels in the brain (1.69 µg/g) and in the testes (1.88 µg/g) were also considerably higher than following intraperitoneal administration during the entire period of observation (15 to 120 min).

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Metabolism of Selegiline [(-)-Deprenyl)]

Cited by 9 publications

References 0 publications

Metabolic Methanol: Molecular Pathways and Physiological Roles

Metabolic Methanol: Molecular Pathways and Physiological Roles

Emerging Role of Safinamide in Parkinson’s Disease Therapy

Monitoring the Level of 14C-Labelled Selegiline Following Oral Administration

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