TY  - JOUR
T1  - Effect of Atomoxetine on Mouse Isolated Vas Deferens Contractility
TT  - Atomoksetitin fare izole vas deferens kontraktilitesi üzerine etkisi
AU  - Engin, Seçkin
AU  - Altınbaş, Mehmet Kağan
PY  - 2024
DA  - October
Y2  - 2024
DO  - 10.33719/nju1538778
JF  - The New Journal of Urology
JO  - New J Urol
PB  - Ali İhsan TAŞÇI
WT  - DergiPark
SN  - 3023-6940
SP  - 129
EP  - 135
VL  - 19
IS  - 3
LA  - en
AB  - Objective: Atomoxetine (ATX), a selective noradrenaline re-uptake inhibitor, is a preferred drug with sufficient efficacy and favorable safety profile for the treatment of  attention-deficit hyperactivity disorder. Ejaculatory dysfunctions have been reported in the patients receiving ATX as sexual side effect, of which underlying mechanisms are largely unknown. The present study aimed to investigate the effect of ATX on mouse isolated vas deferens (VD) contractility as a potential mechanism of ATX-induced ejaculatory dysfunction. Material and Methods: Isolated organ bath studies were performed on prostatic parts of VD obtained from adult male Balb/c mice. The effect of ATX (10-6, 10-5, 3x10-5 and 10-4 M) on KCl (80  mM), phenylephrine (PhE, 3x10-4 M),   adenosine 5’-triphosphate (ATP, 10-2 M) and electrical field stimulation (EFS; 100 V, 64 Hz)-induced contractions of VD strips were evaluated in concentration dependent manner. Results: ATX at 10-6 and 10-5 did not alter the contractile responses (p>0.05), however, higher concentrations of ATX (3x10-5 or 10-4 M) significantly inhibited the KCl, PhE, ATP and EFS-induced contractions of VD strips (p<0.05).  Conclusion: The present study demonstrated for the first time that ATX decreased the contractile responses of mouse isolated VD concentration-dependently. Our results suggest that  ejaculatory dysfunction might be related to the inhibitory effect on ATX on VD.
KW  - atomoxetine
KW  - contraction
KW  - ejaculation
KW  - isolated organ bath
KW  - vas deferens
N2  - Amaç: Seçici bir noradrenalin geri alım inhibitörü olan atomoksetin (ATX), dikkat eksikliği hiperaktivite bozukluğunun tedavisinde yeterli etkinliği ve olumlu güvenlik profiliyle tercih edilen bir ilaçtır. ATX alan hastalarda cinsel yan etki olarak ejakülasyon bozuklukları rapor edilmiştir ve bunların altında yatan mekanizmalar büyük ölçüde bilinmemektedir. Bu çalışma, ATX’e bağlı gelişen ejakülasyon bozukluklarının potansiyel bir mekanizması olarak ATX’in fare izole vas deferens (VD) kontraktilitesi üzerindeki etkisini araştırmayı amaçladı. Gereç ve Yöntemler: Yetişkin erkek Balb/c farelerden elde edilen prostatic VD  striplerinde izole organ banyosu çalışmaları yapıldı. ATX'in (10-6, 10-5, 3x10-5 ve 10-4 M);  KCl (80 mM), fenilefrin (PhE, 3x10-4 M), adenozin 5'-trifosfat (ATP, 10-2 M) ve elektriksel alan stimülasyonu (EAS; 100 V, 64 Hz) ile indüklenen VD kasılmaları üzerine etkisi konsantrasyona bağlı olarak değerlendirildi. Bulgular: 10-6 ve 10-5 M ATX, kasılma yanıtlarını değiştirmedi (p>0.05), ancak daha yüksek ATX konsantrasyonları (3x10-5 veya 10-4 M), KCl, PhE, ATP ve EASile indüklenen önemli ölçüde inhibe etti. Sonuç: Bu çalışma ilk kez ATX'in fare izole VD  kasılma yanıtlarını konsantrasyona bağlı olarak azalttığını gösterdi. Sonuçlarımız ATX’e bağlı gelişen ejakülasyon disfonksiyonunun, ATX'in VD üzerindeki inhibitör etkisi ile ilişkili olabileceğini düşündürmektedir.
CR  - 1. Veronesi GF, Gabellone A, Tomlinson A, Solmi M, Correll CU, Cortese S. Treatments in the pipeline for attention-deficit/hyperactivity disorder (ADHD) in adults. Neurosci Biobehav Rev. 2024;163:105774. https://doi.org/10.1016/j.neubiorev.2024.105774
CR  - 2. Mechler K, Banaschewski T, Hohmann S, Häge A. Evidence-based pharmacological treatment options for ADHD in children and adolescents. Pharmacol Ther. 2022;230:107940. https://doi.org/10.1016/j.pharmthera.2021.107940
CR  - 3. Garnock-Jones KP, Keating GM. Atomoxetine: a review of its use in attention-deficit hyperactivity disorder in children and adolescents. Paediatr Drugs. 2009;11(3):203-226. https://doi.org/10.2165/00148581-200911030-00005
CR  - 4. Kohn MR, Tsang TW, Clarke SD. Efficacy and safety of atomoxetine in the treatment of children and adolescents with attention deficit hyperactivity disorder. Clin Med Insights Pediatr. 2012;6:95-162. https://doi.org/10.4137/ CMPed.S78
CR  - 5. Groom MJ, Cortese S. Current Pharmacological Treatments for ADHD. Curr Top Behav Neurosci. 2022;57:19-50. https://doi.org/10.1007/7854_2022_330
CR  - 6. Steers WD. Physiology of the vas deferens. World J Urol. 1994;12(5):281-285. https://doi.org/10.1007/ BF00191208
CR  - 7. Clement P, Giuliano F. Physiology and Pharmacology of Ejaculation. Basic Clin Pharmacol Toxicol. 2016;119 Suppl 3:18-25. https://doi.org/10.1111/bcpt.1254
CR  - 8. Burnstock G. Purinergic cotransmission. F1000 Biol Rep. 2009;1:46. https://doi.org/10.1016/S0361- 9230(99)00103-3
CR  - 9. Michel MC. Alpha1-adrenoceptors and ejaculatory function. Br J Pharmacol. 2007;152(3):289-290. https:// doi.org/10.1038/sj.bjp.0707369
CR  - 10. Koslov DS, Andersson KE. Physiological and pharmacological aspects of the vas deferens-an update. Front Pharmacol. 2013;4:101. https://doi.org/10.3389/ fphar.2013.00101
CR  - 11. Camporeale A, Day KA, Ruff D, Arsenault J, Williams D, Kelsey DK. Profile of sexual and genitourinary treatmentemergent adverse events associated with atomoxetine treatment: a pooled analysis. Drug Saf. 2013;36(8):663- 671. https://doi.org/10.1007/s40264-013-0074-2
CR  - 12. MacDonald T, Wimalaguna PS, Akosile W. Case report: Severe and treatment-resistant spontaneous ejaculation secondary to atomoxetine. Australas Psychiatry. 2019;27(2):198-199. https://doi.org/10.1177/1039856218815
CR  - 13. Rizvi A, Srinivas S, Jain S. Spontaneous Ejaculation Associated With Atomoxetine. Prim Care Companion CNS Disord. 2022;24(3):21cr03136. https://doi. org/10.4088/PCC.21cr03136.
CR  - 14. Yaylacı F, Şahbudak B, Küçük Ö. Spontaneous Ejaculation Induced with Atomoxetine. Psychopharmacol Bull. 2020;50(1):40-43.
CR  - 15. Gur S, Sikka SC, Knight GE, Burnstock G, Hellstrom WJ. Purinergic contraction of the rat vas deferens in L-NAME-induced hypertension: effect of sildenafil. Asian J Androl. 2010;12(3):415-421. https://doi. org/10.1038/aja.2009.70
CR  - 16. Tanyeri MH, Büyükokuroğlu ME, Tanyeri P, Keleş R, Başarır Bozkurt ŞN, Mutlu O, Akar F, Erden BF, Ulak G. Chronic Effects of Loxapine, Iloperidone, Paliperidone on Mice Isolated Vas Deferens Contractility. OTJHS. March 2022;7(1):40-46. https://doi.org/10.26453/ otjhs.987184
CR  - 17. Banks FC, Knight GE, Calvert RC, Thompson CS, Morgan RJ, Burnstock G. The purinergic component of human vas deferens contraction. Fertil Steril. 2006;85(4):932- 939. https://doi.org/10.1016/j.fertnstert.2005.09.024
CR  - 18. Reed VA, Buitelaar JK, Anand E, et al. The safety of atomoxetine for the treatment of children and adolescents with Attention-Deficit/Hyperactivity Disorder: A comprehensive review of over a decade of research. CNS Drugs. 2016;30(7):603-628. https://doi. org/10.1007/s40263-016-0349-0
CR  - 19. McGrane IR, Campbell TJ. Probable genitourinary adverse events associated with atomoxetine in an adult male: A case report. J Pharm Pract. 2021;34(6):962-965. https://doi.org/10.1177/0897190020953022
CR  - 20. Sivrioglu EY, Topaloglu VC, Sarandol A, Akkaya C, Eker SS, Kirli S. Reboxetine induced erectile dysfunction and spontaneous ejaculation during defecation and micturition. Prog Neuropsychopharmacol Biol Psychiatry. 2007;31(2):548-550. https://doi. org/10.1016/j.pnpbp.2006.10.006
UR  - https://doi.org/10.33719/nju1538778
L1  - https://dergipark.org.tr/tr/download/article-file/4169871
ER  -