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Pharmacological Management of Parkinson’s Disease
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
Newman Osafo, Samuel Obeng, David D. Obiri, Oduro K. Yeboah, Leslie B. Essel
Selegiline can elicit symptomatic effects which is realized in the augmented dopamine presence or its amphetamine metabolites. Nevertheless, the exact mechanism for increasing dopaminergic neurotransmission has not been fully elucidated. This is because MAO-B in the striatum is largely present in glia. In addition, selegiline possesses trophic effects, free of inhibition of MAO-B (Tatton and Greenwood, 1991). Other MAO-B inhibitors include rasagiline.
Dermal and Transdermal Drug Delivery Systems
Published in Tapash K. Ghosh, Dermal Drug Delivery, 2020
Kenneth A. Walters, Majella E. Lane
The efficacy, safety and tolerability of the selegiline transdermal system was determined over a dose range of 6 mg/24 h to 12 mg/24 h in the treatment of major depressive disorder (Feiger et al., 2006). Patients were randomly assigned to blinded treatment with the active or placebo patch for eight weeks, with assessments at weeks 1, 2, 3, 5, 6 and 8. There was significantly greater improvement with the active patch compared to placebo. As in previous trials, the most prominent side effects were application site reactions and insomnia. Amsterdam and Bodkin (2006) presented data from a long-term study that assessed the safety and efficacy of initial and continuation selegiline transdermal therapy (6 mg/24 h) in patients with major depressive disorder. After ten weeks of treatment, patients were randomly assigned to double-blind treatment with transdermal selegiline (6 mg/24 h) or placebo for a year. At the end of the study, significantly fewer treatment patients experienced relapse (16.8%) compared with placebo (30.7%). The early clinical studies on the use of transdermal selegiline in major depressive disorder were reviewed by Culpepper and Kovalick (2008).
Substrates of Human CYP2D6
Published in Shufeng Zhou, Cytochrome P450 2D6, 2018
Selegiline is a drug used for the treatment of early-stage Parkinson’s disease, depression, and senile dementia. Selegiline exhibits little therapeutic benefit when used alone but enhances and prolongs the anti-Parkinson effects of levodopa. At normal clinical doses, it is a selective irreversible MAO-B inhibitor; it also inhibits MAO-A at high doses. Selegiline possesses the classic phenethylamine skeleton with a propargyl group attached to the nitrogen. Both stereoisomers of selegiline are converted to nordeprenyl and L-methamphetamine via N-demethylation and N-depropargylation of the sole basic nitrogen in the molecule by recombinant CYP2D6 (Figure 3.43) (Grace et al. 1994). However, CYP2B6 and 2C19 are the major enzymes for the metabolism of selegiline (Hidestrand et al. 2001). L-Methamphetamine is not considered psychoactive and has little abuse potential, but the stimulatory effect on locomotor activity and dopamine synthesis may be attributed to L-methamphetamine. Selegiline has been classified as a controlled substance in Japan and thus can only be obtained with a prescription or special government license. Selegiline is not a controlled substance in the United States but a prescription is required to obtain it. In February 2006, the US FDA approved Emsam (selegiline), the first transdermal patch for use in treating major depression. Zelapar is a transmucosal preparation for human administration of selegiline.
Manganese concentration in patients with encephalopathy following ephedrone use: a narrative review and analysis of case reports
Published in Clinical Toxicology, 2022
Michal Ordak, Natalia Sloniewicz, Tadeusz Nasierowski, Elzbieta Muszynska, Magdalena Bujalska-Zadrozny
de Bie et al. described the case of a 36-year-old man from Azerbaijan who noticed a decrease in his libido in 2005 [18]. In 2004, the patient began to self-inject a methcathinone solution prepared by combining pseudoephedrine hydrochloride with potassium permanganate. He used this solution one to two times a day. Soon after, the patient experienced excessive sleepiness and slowness of movement. These symptoms progressed rapidly for the first few months and then stabilized. The patient was difficult to understand due to palilalia. He did not drool but occasionally choked. He had difficulty walking but reported no problems with maintaining his balance. He had restless legs syndrome (RLS). The patient experienced difficulties in performing fine motor movements but had no gastrointestinal symptoms. The patient's manganese content was measured in whole blood (897 nmol/L) and urine (2804.3 nmol/24 h). Pramipexole dihydrochloride in doses up to 75 mg/day had no effect on Parkinsonism but relieved his RLS. He stopped taking this due to excessive daytime sleepiness and a craving for sweets. Selegiline hydrochloride and levodopa-carbidopa at doses of up to 600/150 mg/day were unsuccessful. Thereafter, a naturopathic physician treated him with a series of calcium disodium EDTA infusions without effect on his symptoms [18].
Complications of levodopa therapy in Parkinson’s disease
Published in Expert Opinion on Orphan Drugs, 2019
Jordan Dubow, C. Warren Olanow
There are currently three approved MAO-B inhibitors for the treatment of motor fluctuations in PD, selegiline, rasagiline and safinamide. Selegiline is available as a twice a day tablet or a once daily orally disintegrating tablet and has demonstrated a reduction in OFF time of approximately 1-hour compared to placebo [26]. Rasagaline, a once-daily, second generation highly-selective MAO-B inhibitor, is also effective for the treatment of ‘Off’ time and also reduces ‘Off’ time by approximately 1-hour compared to placebo [27,28]. Safimamide, a MAO-B inhibitor which also blocks activated sodium channels and thereby reduces calcium-mediated glutamate release, was recently approved by the FDA for the treatment of motor fluctuations. Similar to the other MAO-B inhibitors, safinamide has been shown to increase ‘On’ time without troublesome dyskinesia and reduce ‘Off’ time by approximately one hour [29].
Design of selegiline-loaded bio-nanosuspension for the management of depression using novel bio-retardant from Manilkara zapota
Published in Drug Development and Industrial Pharmacy, 2019
Yogita Tyagi, N. V. Satheesh Madhav
Depression is a common mental illness affecting over 300 million people worldwide and is expected to be a major contributor of the global diseases burden by 2030. The disorder impacts on the family and socioeconomic aspects of patients’ lives as well as imposes a huge financial impact on communities, employers, health care systems, and general government budgets [1]. Monoamine oxidase (MAO) inhibitors had been used for treatment of depression in the late 1950s, and some of them are still prescribed today despite the introduction of new class antidepressants [2]. Selegiline is a preferential MAO-B inhibitor that is currently used as an adjunct therapy to treat late stage Parkinson's disease. Monoamine oxidase is an enzyme which accelerates the breakdown of dopamine. In addition, placebo controlled clinical trials have shown it to have effective antidepressant activity [3–5]. At therapeutic doses up to 10 mg/day orally for PD, selegiline can be safely administered without the need for a tyramine restricted diet. Oral selegiline may be an effective antidepressant [6,7] at doses in excess of 20 mg daily when enzyme selectivity is lost (MAO-A is inhibited in addition to MAO-B), thus necessitating tyramine dietary restrictions [8,9].