Depresyon Tedavisinde Dihidropiridin Türevi Kalsiyum Kanal Blokerlerinin Önemi

Abstract

DSM IV kriterlerine göre iki haftadan daha uzun süren, çökkün duygudurum ya da günlük aktivitenin etkilenmesi depresyon olarak kabul edilir. Depresyon patofizyolojisi ve antidepresanların etki mekanizmaları ile ilgili artan bilgi birikimine rağmen, hastalığın tedavisine yüksek oranda cevap alınamaması ve bu cevabın da gecikmeyle görülmesi gibi klinik sorunlar nedeniyle, bu alanda yapılan preklinik çalışmalar önemini korumaktadır. Antidepresan etkili ajanların çoğu sinaptik aralıkta serotonin ya da norepinefrin geri alınımını baskılayarak etki gösterirler, fakat başka ilgisiz reseptörlere de bağlandıkları için birçok yan tesire sebebiyet verirler. Depresyonda kalsiyum iyonu regulasyonu bozulmuştur. Dihidropiridin türevi kalsiyum kanal antagonistleri farelerde davranışsal çaresizlik testlerinde araştırılmıştır. Sonuçlara göre dihidropiridinlerin antidepresan etkinliği olabilir. 

Keywords

• Depresyon,Dihidropiridin,Antidepresan

Importance of The Dıhydropyrıdıne Types Calcıum Canal Blokers on The Depressıon Treatment

Abstract

According to the DSM IV, a person who suffers from depressive disorder must either have a depressed mood or a loss of interest or pleasure in daily activities consistently for at least a two week period. In spite of our increasing knowledge about the pathophysiology of depression and the mechanisms of antidepressant treatments, there are some unmet clinical needs like the high rate of lack of response to antidepressants and the time lag before the action of conventional therapeutics. Many agents with effective antidepressant agents action amplify serotonin or norepinephrine signaling by inhibiting reuptake at the synaptic cleft, but they also have many side-effects due to binding to unrelated receptors. Calcium ion is dysregulated in depression. The dihydropyridine calcium channel antagonists in the mouse behavioral despair test was investigated. According to the results there has been affirm that dihydropyridine's may have antidepressant efficacy.

Keywords

• Depression,Dihydropyridine,Antidepressant

References

1. 1. Örsel S. Depresyonda Tedavi: Genel ilkeler ve Kullanılan Antidepresan İlaçlar. Klinik Psikiyatri 2004;4:17-24.
2. 2. Mann JJ. Drug therapy. The medical management of depression. New Engl J Med 2005;353:1819-34.
3. 3. Levinson DF. The genetics of depression: Review Biol Psychiat 2006;60:84-92.
4. 4. Kalia M. Neurobiological basis of depression: an update. Metabolism 2005;54:24-7.
5. 5. Umemiya M, Berger AJ. Single-Channel properties of four calcium channel types in rat motoneurons. J neurosci 1995;15:2218-24.
6. 6. Paul IA. Antidepressant activity and calcium signalingcascades. Hum Psychopharmacol 2001;16:71- 80.
7. 7. Frye MA, Pazzaglia PJ, George MS et al. Low CSF somatostatin associeted with response to nimodipine in patents with affective illness. Biol Psychiat 2003;53:180-3.
8. 8. Benedetti F, Bernasconi A, Pontggia A. Depression and neurological disorders. Curr Opin Psychiatry 2006;19:14-8.

9. 9. Levy NA, Janicak PG. Calcium channel antagonists for the treatment of bipolar disorder. Bipolar Disord 2000;2:108-19.
10. 10. Goodnick PJ. The use of nimodipine in the treatment of mood disorders. Bipolar Disord 2000;2:165-73.
11. 11. Felker BL, Hedrick SC, Chaney EF, Liu CF, Heagerty P, Caples H, Lin P, Katon W. Identifying Depressed Patients With a High Risk of Comorbid Anxiety in Primary Care. Prim Care Companion J Clin Psychiatry. 2003 Jun;5(3):104-110.
12. 12. Kayaalp O. Tıbbi Farmakoloji ( 12. baskı ) Hacettepe-Taş yayınevi, Ankara 2009, ss. 770-795.
13. 13. Anderson IM. The new antidepressants. Current Anaesthesia & Critical Care 1999; 10: 32-39.
14. 14. Kennedy SA. A review of antidepressant treatments today. Eur Neuropsychopharm 2006;6:619-24.
15. 15. Kent JM. SNaRIs, NaSSAs, and NaRIs: new agents for the treatment of depression. The Lancet 2000;355:911-18.
16. 16. Mogilnicka E, Czyrak A, Maj J. Dihydropyridine calcium channel antagonists reduce immobility in the mouse behavioral despair test; antidepressants facilitate nifedipine action. Eur J Pharmacol 1987;138:413-6.
17. 17. Cohen C, Perrault G, Sanger DJ. Effects of dihydropyridine Ca2+ channel blockers on the discriminative stimulus and the motor impairing effects of (±)-Bay K 8644. Eur J Pharmacol 1997;336:113-21.
18. 18. Czyrak A, Mogilnicka E, Maj J. Dihydropyridine calcium channel antagonists as antidepressant drugs in mice and rats. Neuropharmacology 1989;28:229-33.
19. 19. Pazzaglia PJ, Post RM, Ketter TA et al. Nimodipine monotherapy and Carbamazepine augmentation in patients with refractory recurrent affective illness. J Clin Psychopharm 1998;18:404-13.
20. 20. Srivastava SK, Nath C. The differantial effect of calcium channel blockers in the behavioural depair test in mice. Pharmacol Res 2000;42:4.
21. 21. Wojciech K, Wanda D, Olgierd P. Activity of diltiazem and nifedipine in some animal models of depression. Pol J Pharmacol Pharm 1990;42:121-7.
22. 22. Katz AM, Leac NM. Differential effects 1,4- dihydropyridine calcium channel blockers: therapeutic implications. J Clin Pharmacol 1987; 27: 825-34.
23. 23. Blardi P, Urso P, de Lalla A, Volpi L, Di Peri T, Auteri A. Nimodipine: Drug pharmacokineticks and plasma adenosine levels in patients affected by cerebral ischemia. Clin Pharmacol Ther 2002;72:556-62.
24. 24. Lindberg G, Bingefors K, Jonas LR, Melander A. Use of calcium channel blockers and risk of suicide: ecological findings populations based cohort study. Brit Med J 1998;316:741-5.
25. 25. Ried LD, Tueth MJ, Handberg E et all. A study of antihypertensive drugs and depressive symptoms ( SADDSx) in patients treated with a calcium Antagonist versus an atenolol hypertension treatment strategy in the international verapamil SR-Trandolapril study. Psychosom Med 2005;67:398-406.
26. 26. Dunn NR, Freemantle SN, Mann RD. Cohort study calcium channel blockers, other cardiovascular agents, and the prevalence of depression. J Clin Pharmacol 1999;48:230-3.
27. 27. Rogoz Z, Skuza G. Mechanism of synergistic action following co-treatment with pramipexole and fluoxetine or sertaline in the forced swimming test in rats. Pharmacol Rep 2006;58:493-500.