MAO-B inhibitors, Selegiline to Rasagiline 전환

MAO-B inhibitors

마오비 정

아질렉트 정

성분명	Selegiline	Rasagiline
상품명	마오비 정	아질렉트 정
함량	5 MG	1 MG
효능/효과	1. 초기 파킨슨증후군의 단독요법 (레보도파 치료시작 시기 연장). 2. 레보도파 제제와 병용투여 시 레보도파의 효과를 증가, 지속(레보도파 감량 가능).	특발성 파킨슨병의 치료: 1. 초기 단독요법 또는 도파민 효능제의 보조요법 2. 운동 동요 증상(end of dose fluctuations)이 있는 환자에서 레보도파의 보조요법
용법용량 (국내)	5-10 mg/day (아침, 점심) max 10 mg/day	1 mg qd (levodopa 병용 중인 환자에게 권장되는 초기 용량 0.5 mg qd)
용법용량 (Lexicomp)	파킨슨병 - 5-10 mg/day (아침, 점심) - max 10 mg/day - carbidopa/levodopa와 병용 시, levodopa의 용량 10-30 % 감량, selegiline 지속 복용시, 추가적인 감량 고려 우울증 - transdermal 제형 (oral보다 부작용을 유발하는 대사체의 생성 적음)	파킨슨병 - monotherapy or adjunctive therapy (not including levodopa) : 1 mg qd - adjunctive therap with levodopa : 0.5 mg qd → 1 mg qd - max 1 mg/day - levodopa와 병용 시, levodopa를 9-13% 정도 감량 고려
약리작용	irreversible selective MAO-B inhibitor (고용량에서 MAO-B selectivity 상실)	irreversible selective MAO-B inhibitor
대사체	amphetamine & methamphetamine (active) the other (inactive)	aminoindan (weak MAO-B inhibitor) ; no amphetamine-like properties
반감기	10 hr	~3 hours (no correlation with biologic effect due to irreversible inhibition) *반감기는 짧지만 duration은 1 wk 정도임
배설	Urine	Urine
비고	SSRIs, SNRIs, triptans, TCAs, fentanyl, lithium, tramadol, buspirone, St John's wort 등의 serotonergic agent와 병용 시, serotonin syndrome 발생에 유의	selegiline보다 10배 더 potent aminoindan : neuroprotective effect
부작용	두통(18%; ODT: 7%; oral: 4%), 어지러움(oral: 14%; ODT: 11%), 수면장애(12%; ODT: 7%), 구역, 구토 섬망(oral: 6%; ODT: 4%)	두통 (14%), 섬망 (1%) * selegiline에 비해 신경계 부작용이 덜 함

* MAO inhibitors : linezolid & intravenous methylene blue

 

selegiline to rasagiline 전환

Switch from selegiline to rasagiline is beneficial in patients with Parkinson’s disease

rasagiline의 neuroprotective effect : NMDA receptor antagonist ; enhance motor complications and have a moderate beneficial effect on motor symptoms in PD patients

 

초록 : The objective of this study is to demonstrate that application of rasagiline instead of selegiline with concomitant determination of L-amphetamine and L-methamphetamine in plasma is safe and well tolerated and influences sleep, mood, and motor behavior in patients with Parkinson’s disease on a stable drug therapy. 30 patients, who took 7.5 mg selegiline daily for at least 3 months, were switched to 1 mg rasagiline. Then they were followed over an interval of 4 months. The remaining drug therapy remained stable. This changeover was safe and well tolerated. L-Amphetamine and L-methamphetamine only appeared during selegiline treatment. Motor behavior, motor complications, mood and sleep improved during rasagiline administration. Amphetamine-like derivatives of selegiline could contribute to sleep disturbances, which may be involved in worsening of mood. Motor behavior and motor complications probably became better due to the additional glutamate receptor antagonizing properties of rasagiline in this open label study.

 

 

결론 : We show that a switch from Se to Ra is well tolerated and safe. This changeover may provide a certain benefit for PD patients in terms of occurrence of certain non-motor features and of motor behavior. This trial emphasizes that the choice of drugs for the treatment of motor behavior may also have implications on the appearance and the intensity of non-motor symptoms in PD.

 

reference : 

(1) lexicomp

(2) Müller, Thomas, et al. "Switch from selegiline to rasagiline is beneficial in patients with Parkinson’s disease." Journal of Neural Transmission 120.5 (2013): 761-765.