Loksapin, İloperidon, Paliperidon'un İzole Farelerde Vas Deferens Kasılması Üzerine Kronik Etkileri

Öz

Amaç: Erektil disfonksiyon, antipsikotiklerin olağan bir yan etkisidir; bu da hastaların ilaç kullanmaktan kaçınmasına neden olur. Bu çalışmanın amacı iloperidon, paliperidon ve loksapin'in farelerde serotonin (5-HT), noradrenalin (NA), adenozin trifosfat (ATP) ve potasyum klorür (KCl) ile indüklenen vas deferens kasılmaları üzerine etkilerini araştırmaktır.
Materyal ve Metot: Fareler rastgele deney gruplarına ayrıldı ve 21 gün boyunca ip enjeksiyonu ile tedavi edildi. Tedaviden sonra, ilaçların farelerin vas deferens şeritlerinin epididimal ve prostatik bölümlerinde 5-HT, ATP, NA ve KCl ile indüklenen kasılma tepkileri üzerindeki etkileri araştırıldı.
Bulgular: İloperidon, paliperidon ve loksapin ile tedavi edilen gruplardan elde edilen vas deferensin her iki bölümünde 5-HT ile indüklenen kasılma tepkileri önemli ölçüde artarken ATP ile indüklenen kasılma tepkileri önemli ölçüde azaldı. Bununla birlikte, bu ilaçların, fare vas deferens'in NA ve KCl ile indüklenen kasılmaları üzerinde önemli bir etkisi olmamıştır.
Sonuç: Bu sonuçlar, iloperidon, paliperidon ve loxapin'in kronik tedavilerinden serotonin ve ATP kaynaklı vas deferens kasılmalarının etkilendiğini göstermiştir. Bu ilaçlarla kronik olarak tedavi edilen farelerde, serotonerjik ve purinerjik reseptörler, erektil disfonksiyona neden olan vas deferens kasılmalarındaki değişikliklere katkıda bulunabilir. 

Anahtar Kelimeler

• Erektil disfonksiyon
• Erektil disfonksiyon
• iloperidon
• in vitro
• loksapin
• paliperidon

Chronic Effects of Loxapine, Iloperidone, Paliperidone on Mice Isolated Vas Deferens Contractility

Abstract

Objective: Erectile dysfunction is a usual side effect of antipsychotic medications; this causes patients to avoid using drugs. The aim of this study to investigate the effects of iloperidone, paliperidone and loxapine on serotonin (5-HT), noradrenaline (NA), adenosine triphosphate (ATP) and potassium chloride (KCl)-induced contractions of the vas deferens in mice.
Materials and Methods: The mice were randomly divided into experimental groups and treated by ip injection of drugs for 21 days. After the treatment, the effects of drugs were investigated on 5-HT, ATP, NA and KCl-induced contractile responses in the epididymal and prostatic portions of mice vas deferens strips.
Results: 5-HT-induced contractile responses were significantly increased while ATP-induced contractile responses were significantly decreased in the both portions of the vas deferens obtained from the iloperidone, paliperidone and loxapine-treated groups. However, these drugs had no significant effect on NA- and KCl-induced contractions of mice vas deferens.
Conclusion: These results showed that serotonin and ATP-induced contractions of vas deferens were affected by the chronic treatments of iloperidone, paliperidone, and loxapine. In mice chronically treated with these drugs, serotonergic and purinergic receptors may contribute to changes in vas deferens contractions that cause erectile dysfunction. 

Keywords

• iloperidone
• paliperidone
• loxapine
• Erectile dysfunction
• in vitro

Kaynakça

1. Kissi Y, Mannai J, Laroussi M, et al. Sexual Function in Untreated then Treated Schizophrenic Patients: A prospective study. European Psychiatry. Eur Psychiat. 2011;26:1378-1378.
2. Baggaley M. Sexual dysfunction in schizophrenia: focus on recent evidence. Hum Psychopharmacol. 2008;23(3):201-209. doi:10.1002/hup.924.
3. Montejo Montejo ÁL, Majadas S, Rico-Villademoros F, et al. Frequency of sexual dysfunction in patients with a psychotic disorder receiving antipsychotics. J Sex. 2010;7(10):3404-3413.
4. Zemishlany Z. the Impact of Psychiatric Disorders on Sexual Dysfunction: An Update. European Psychiatry, AS01-02 -2012;27(S1)1-1. doi:10.1016/S0924-9338(12)73952-4
5. Althof SE, Leiblum SR, Chevret-Measson M, et al. Psychological and interpersonal dimensions of sexual function and dysfunction. J Sex. 2005;2(6):793-800.
6. Clayton AH, Alkis AR, Parikh NB, Votta JG. Sexual Dysfunction Due to Psychotropic Medications. Psychiatr Clin North Am. 2016;39(3):427-463.
7. Waldinger MD. Psychiatric disorders and sexual dysfunction. Handb Clin Neurol 2015;130:469-489.
8. Alwaal A, Breyer BN, Lue TF. Normal male sexual function: emphasis on orgasm and ejaculation. Fertil Steril. 2015;104(5):1051-1060. doi:10.1016/j.fertnstert.2015.08.033

9. Caccia S, Pasina L, Nobili A. New atypical antipsychotics for schizophrenia: iloperidone. Drug Des Devel Ther. 2010;4:33-48.
10. Tonin FS, Wiens A, Fernandez-Llimos F, Pontarolo R. Iloperidone in the treatment of schizophrenia: an evidence-based review of its place in therapy. Core Evid. 2016;11:49-61.
11. Bioque M, Parellada E, García-Rizo C, et al. Clozapine and paliperidone palmitate antipsychotic combination in treatment-resistant schizophrenia and other psychotic disorders: A retrospective 6-month mirror-image study. Eur Psychiatry. 2020;63(1):e71. doi:10.1192/j.eurpsy.2020.72.
12. Faden J, Citrome L. Examining the safety, efficacy, and patient acceptability of inhaled loxapine for the acute treatment of agitation associated with schizophrenia or bipolar I disorder in adults. Neuropsychiatr Dis Treat. 2019;15:2273-2283.
13. Djillani A, Mazella J, Heurteaux C, Borsotto M. Role of TREK-1 in Health and Disease, Focus on the Central Nervous System. Front Pharmacol. 2019;10:379. doi:10.3389/fphar.2019.00379
14. Ho CC, Singam P, Hong GE, Zainuddin ZM. Male sexual dysfunction in Asia. Asian J Androl. 2011;13(4):537-542.
15. Yafi F, Jenkins L, Albersen M et al. Erectile dysfunction. Nat Rev Dis Primers 2. 2016;16003.
16. Calabrò RS, Cacciola A, Bruschetta D, et al. Neuroanatomy and function of human sexual behavior: A neglected or unknown issue?. Brain Behav. 2019;9(12):e01389. doi:10.1002/brb3.1389
17. Atmaca M. Selective Serotonin Reuptake Inhibitor-Induced Sexual Dysfunction: Current Management Perspectives. Neuropsychiatr Dis Treat. 2020;16:1043-1050.
18. Steers WD. Pharmacologic treatment of erectile dysfunction. Rev Urol. 2002;4(3):17-25.