Uluhlu olubanzi lukaSelegiline lweziPhumo zokuNyanga ezinokubakho

I-Selegiline yi-monoamine oxidase (MAO) B inhibitor engaguqulekiyo¹. I-monoamine neurotransmitters, njenge-serotonin, dopamine kunye ne-norepinephrine, zizinto eziphuma kwi-amino acids². I-enzyme i-monoamine oxidase A (MAO A) ngokuyinhloko i-oxidise (iqhekeza) i-serotonin kunye ne-norepinephrine engqondweni, ngelixa i-monoamine oxidase B (MAO B) i-oxidises phenylethylamine, i-methylhistamine kunye ne-tryptamine.³. I-MAO A kunye ne-B zombini zichitha i-dopamine kunye ne-tyramine³. Ukuthintela i-MAOs kwandisa inani le-monoamine neurotransmitters kwingqondo ngokuthintela ukuphuka kwazo.³. I-MAO inhibitors (i-MAOIs) inokukhetha nokuba kukwahluka kwe-A okanye kwe-B ye-enzyme kwiidosi eziphantsi kodwa ithande ukulahlekelwa ukukhetha kwi-MAO ethile kwiidosi eziphezulu.³. Ngaphaya koko, ii-MAOIs zinokubophelela kwi-MAO ngokubuyisela umva okanye ngokungenakujikwa ukuthintela isenzo se-enzyme.⁴, kunye neyokugqibela ithande ukuba namandla ngakumbi.

I-MAOIs iyancipha ekusebenziseni ixesha elide ngenxa yokuphuhliswa kweziyobisi ezijolise ngokukhethekileyo kwii-neurotransmitters ezahlukeneyo, njengoko i-MAOIs inokubangela ukunyuka kwetyramine ngenxa yokuthintela ukuphuka kwayo, kunye ne-tyramine-induced crisis hypertension ingenzeka.⁵. Ngenxa yalo mngcipheko, ukutya kwesigulana kufuneka kubekwe iliso elibukhali lokutya okutyebileyo kwetyramine okungalunganga, kwaye uninzi lwentsebenziswano yeziyobisi lunokwenzeka xa i-MAOI isetyenziswa nelinye iyeza elichaphazela amanqanaba e-neurotransmitter anokuba yingozi njengakwimeko zoxinzelelo olukhulu. i-serotonin ephezulu, okanye i-serotonin syndrome⁶.

I-Selegiline yinto yakudala efunyenweyo, kwaye yaqala ukwenziwa ngo-1962¹. Ijolise ngokukhethekileyo kwi-MAO B kwiidosi eziphantsi, kwaye kwakhona ayibonakali inyusa ngokuyingozi amanqanaba etyramine ebangela xi nzelelo xa udibene nokutya okutyebileyo kwetyramine; endaweni yoko, kunciphisa uxinzelelo lwegazi ngokubanzi¹. Ngaphaya koko, ayisiyotyhefu yesibindi kwaye ibonakala inyusa ixesha lokuphila kwi Isifo sikaParkinson (PD) izigulane¹. Kuphononongo, yalibazisa imfuno ye-levodopa kwi-PD malunga neenyanga ezili-9 xa ithelekiswa ne-antioxidant tocopherol, mhlawumbi ngenxa yeziphumo zokwanda kwe-dopamine yechiza njengoko kubonwa kwi-post-mortem brains of selegiline-izigulane ezinamazinga aphezulu e-dopamine.¹. Ukongeza, i-selegiline ngokwayo inciphisa uxinzelelo lwe-oxidative olusebenza njenge-neuroprotectant kunye nomsebenzi we-neurotrophic kunye ne-antiapoptotic.¹.

I-Selegiline ikwaphucula imisebenzi yeemoto, imisebenzi yememori kunye nobukrelekrele kwizigulana zePD⁷. Kubantwana abanengxaki yokungahoywa/yokungakhathali (ADHD), i-selegiline yanciphisa iimpawu ze-ADHD ngokuphucula indlela yokuziphatha, ingqalelo kunye nokufunda kolwazi olutsha ngaphandle kweziphumo ebezingalindelekanga eziphawuliweyo.⁸. Kulutsha olunoxinzelelo, ukuncipha okukhulu kweempawu zokudakumba kubonwa kusetyenziswa i-selegiline yolawulo lwe-transdermal.⁹. Xa isetyenziselwa ukunyanga ingxaki enkulu yoxinzelelo (MDD), kunokuba ibangele iziphumo ebezingalindelekanga zesondo njenge-serotonin exposure-yandisa antidepressants.¹⁰, i-selegiline ibe nefuthe elihle lokwandisa amanqaku kwiimvavanyo ezininzi zesondo¹¹ kunokwenzeka ngenxa yeziphumo zayo ze-dopaminergic.

I-MAO-B inhibitors ezifana ne-selegiline kunye ne-rasagiline zikholisa ukucothisa isantya sokuqhubeka kwezifo ze-neurodeergenerative.¹, kwaye zombini zikholisa ukuba nokusebenza okufanayo ekuphatheni iPD¹². Nangona kunjalo, kwimodeli yeempuku, i-selegiline isebenzise iziphumo ezichasayo ngokungafaniyo ne-rasagiline naxa omabini amachiza ayefaniswe idosi ye-MAO inhibition.¹³, icebisa nokuba i-non-MAO inhibition inxulumene neenzuzo ezinxulumene ne-selegiline. I-Selegiline ikwandise iplastiki ye-synaptic kwi-medial prefrontal cortex yeempuku ezine-PD efanisiweyo.¹³, okunokwenzeka ngenxa yesiphumo esihle esijongiweyo sechiza kwizinto ze-neurotrophic ezifana ne-nerve factor, i-brain-derived neurotrophic factor kunye ne-glial cell-derived neurotrophic factor.¹⁴. Ekugqibeleni, i-selegiline inokwahlulwa njenge-MAOI ekhethekileyo ngenxa ye-metabolites enomdla equka i-l-amphetamine-like kunye ne-l-methamphetamine.¹⁵, enokuba negalelo kwiziphumo ezizodwa ze-selegiline. Ngaphandle kwezi metabolites, kuye kwacetyiswa ukuba kusetyenziswe ukunyanga ukusetyenziswa kakubi kwe-psychostimulant kunye nokuyeka ukutshaya njengoko i-selegiline ikholelwa ukuba inamandla okuxhatshazwa okuphantsi kwimeko yeklinikhi.¹⁵.

***

Iingxelo:  

1. Tábi, T., Vécsei, L., Youdim, MB, Riederer, P., & Szökő, É. (2020). I-Selegiline: I-molecule enobuchule obutsha. Ijenali yosasazo lwe-neural (iVienna, Ostriya : 1996), 127(5), 831-842. https://doi.org/10.1007/s00702-019-02082-0 

2. Inzululwazi Ngqo 2021. Monoamine. Iyafumaneka kwi-intanethi https://www.sciencedirect.com/topics/medicine-and-dentistry/monoamine  

3. I-Sub Laban T, i-Saadabadi A. I-Monoamine Oxidase Inhibitors (MAOI) [Ihlaziywe ngo-2020 ngo-Agasti 22]. Ku: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Ifumaneka kwi: https://www.ncbi.nlm.nih.gov/books/NBK539848/ 

4. URudorfer MV. I-Monoamine oxidase inhibitors: iyabuyiselwa kwaye ayinakuguqulwa. Psychopharmacol Bull. 1992;28(1):45-57. PMID: 1609042. Ifumaneka kwi-intanethi https://pubmed.ncbi.nlm.nih.gov/1609042/  

5. Sathyanarayana Rao, TS, & Yeragani, VK (2009). Ingxaki yoxinzelelo lwegazi kunye ushizi. Ijenali yaseIndiya yezengqondo, 51(1), 65-66. https://doi.org/10.4103/0019-5545.44910 

6. INzululwazi Ngqo 2021. Monoamine Oxidase Inhibitor. Iyafumaneka kwi-intanethi https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/monoamine-oxidase-inhibitor  

7. Dixit SN, Behari M, Ahuja GK. Impembelelo ye-selegiline kwimisebenzi yokuqonda kwisifo sikaParkinson. J Assoc OoGqirha baseIndiya. 1999 Aug;47(8):784-6. PMID: 10778622. Ifumaneka kwi-intanethi apha https://pubmed.ncbi.nlm.nih.gov/10778622/  

8. Rubinstein S, Malone MA, Roberts W, Logan WJ. Uphononongo olulawulwa yi-Placebo oluvavanya iziphumo ze-selegiline kubantwana abanengxaki yokungahoywa/i-hyperactivity disorder. J Umntwana Ofikisayo kwiPsychopharmacol. 2006 Aug;16(4):404-15. DOI: https://doi.org/10.1089/cap.2006.16.404  I-PMID: 16958566.  

9. DelBello, MP, Hochadel, TJ, Portland, KB, Azzaro, AJ, Katic, A., Khan, A., & Emslie, G. (2014). Uphononongo oluphindwe kabini olungaboniyo, olulawulwa yi-placebo lwenkqubo ye-selegiline transdermal kulutsha oludandathekileyo. Ijenali yomntwana kunye ne-psychopharmacology yolutsha, 24(6), 311–317. DOI: https://doi.org/10.1089/cap.2013.0138 

10. Jing, E., & Straw-Wilson, K. (2016). Ukungasebenzi ngokwesondo kwi-serotonin reuptake inhibitors (SSRIs) ekhethiweyo kunye nezisombululo ezinokubakho: Uphononongo loncwadi olubalisayo. Ugqirha wempilo yengqondo, 6(4), 191–196. DOI: https://doi.org/10.9740/mhc.2016.07.191 

11. Clayton AH, Campbell BJ, Favit A, Yang Y, Moonsammy G, Piontek CM, Amsterdam JD. Iimpawu zokungasebenzi kakuhle ngokwesondo kwizigulana eziphathwe ngenxa yoxinzelelo olukhulu: uhlalutyo lwe-meta oluthelekisa inkqubo ye-selegiline ye-transdermal kunye ne-placebo usebenzisa isikali esilinganiswe nesigulana. J Clin Psychiatry. 2007 Dec;68(12):1860-6. DOI: https://doi.org/10.4088/jcp.v68n1205 . PMID: 18162016. 

12. Peretz, C., Segev, H., Rozani, V., Gurevich, T., El-Ad, B., Tsamir, J., & Giladi, N. (2016). Ukuthelekiswa kweSelegiline kunye neRasagiline Therapies kwi-Parkinson Disease: Isifundo sobomi bokwenyani. I-neuropharmacology yeklinikhi, 39(5), 227–231. DOI: https://doi.org/10.1097/WNF.0000000000000167  

13. Okano M., Takahata K., Sugimoto J kunye ne-Muraoka S. 2019. I-Selegiline Ibuyisela kwakhona i-Synaptic Plasticity kwi-Medial Prefrontal Cortex kwaye iphucula i-Depression-Ned Behaviour in the Mouse Model of Parkinson's Disease. Ngaphambili. Ukuziphatha. Neurosci., 02 Agasti 2019. DOI: https://doi.org/10.3389/fnbeh.2019.00176  

14. I-Mizuta I, i-Ohta M, i-Ohta K, i-Nishimura M, i-Mizuta E, i-Hayashi K, i-Kuno S. Selegiline kunye ne-desmethylselegiline ivuselela i-NGF, i-BDNF, kunye ne-GDNF synthesis kwi-astrocyte ye-mouse ekhulisiwe. I-Biochem Biophys Res Commun. 2000 Dec 29;279(3):751-5. doi: https://doi.org/10.1006/bbrc.2000 . 4037. PMID: 11162424. 

15. Yasar, S., Gaál, J., Panlilio, LV, Justinova, Z., Molnár, SV, Redhi, GH, & Schindler, CW (2006). Ukuthelekiswa kokuziphatha kweziyobisi ezigcinwe yi-D-amphetamine, L-deprenyl (selegiline), kunye ne-D-deprenyl phantsi kweshedyuli yesibini kwi-squirrel monkey. Psychopharmacology, 183(4), 413-421. https://doi.org/10.1007/s00213-005-0200-7 

***