jurnalul român de psihofarmacologie romanian journal of ...

jurnalul român de psihofarmacologie romanian journal of ... jurnalul român de psihofarmacologie romanian journal of ...

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07.02.2013 Views

Acţtiunile farmacologice ale antidepresivelor vor produce modificări şi schimbări semnificative în mesagerii secundari, în expresia genelor precoce şi precocissime, în sinteza proteinelor, în modificările de sinaptogeneză şi neurogeneză, de metabolisme cerebrale, activitate celulară glială, de secreţie a hormonului de stress, de echilibru între factorii neuroendocrini şi factorii neuroimunologici şi expresia genelor neuropeptidice. Un efect comun mai multor tipuri de terapie asociată ca aplicarea deprivării de somn, terapie electroconvulsivantă, a medicaţiei psihotrope antidepresive, implică procesul de „downregulation” al mesagerului acidului ribonucleic (mARN) al corticotropin-releasing-hormonului şi procesul de „up-regulation” al mARN al receptorului glucocorticoid din hipotalamus, două procese ce reflectă un feed-back negativ asupra activităţii axei hipotalamo-hipofizo-suprarenale. O întrebare provocatoare cu consecinţe imediate şi de perspectivă apropiată va fi să stabilim ordinea şi prioritatea modificărilor reprezentănd acţiunile primare ale antidepresivelor şi care sunt consecinţele modificărilor secundare ale acţiunii unor molecule terapeutice cu diverse mecanisme modale de acţiune asupra diverselor ţinte, dar şi a efectelor de ordin practic şi clinic asupra pacientului aflat în tratament (vezi tabelul 2). Inhibitori ai COMT Molecule de ISRS ce antagonizează receptorii 5-HT1A presinaptici (dendritici) Modularea compuşilor endogeni ce inhibă eliberarea 5-HT Tabel 2. Modalităţi de acţiune a noilor potenţiale antidepresive Catecol-o-metil-transferaza este enzima ce participă în catabolismul monoaminelor Vor împiedica creşterea serotoninei în spaţiul interstiţial prin inhibiţia receptorilor 5-HT1A Există un ligand endogen ce are efcte de ISRS. Modularea acestui ligand poate efectua acţiuni de tip antidepresiv Modularea melatoninei Agoniştii melatoninici pot acţiona cu efect antidepresiv Inhibarea axei HPTA Antagoniştii de CRH au rol antidepresiv. Inhibitorii sintezei cortizolului – ketoconazolul sau metyrapona au efecte antidepresive. Vasopresina stimulează secreţia corticotropinică (ACTH) Urocortina – afinitate pentru receptorii CRH Modularea sistemului colinergic Receptorii nicotinergici au acţiune modulatorie.Agoniştii nicotinergici au efecte antidepresive. Modularea sistemului GABA-ergic Agonişti inverşi ai receptorilor centrali BZD-potenţiali antidepresivi Modularea receptorilor neuropeptidici sau ai enzimelor catabolice MK 869- antagonist al NK1, dar alţi antagonişti de substanţă P sunt pe cale de elaborare. Captopril – efect antidepresiv prin inhibarea peptidazei ce metabolizează opioizii endogeni. Modulatorii de mesageri secundari Rolipram este un inhibitor de fosfodiesterază de tip 4 (influenţează protein kinazele) Alţii Antagoniştii receptorilor citokinici- efect antidepresivi bazaţi pe ipoteza inflamatorie a depresiei. Modafinil: subpresor de somn paradoxal dă deprivare de somn Antagonişti de receptori adenozinici. Glutamatul şi neurotransmisia GABA-ţinte pentru noile antidepresive 38

Bibliografie 1. Frank E, Prien RF, Jarrett RB et al, 1991 – Conceptualization and rationale for consensus definitions of terms in major depressive disorder: remission, recovery, relapse and recurrence. Arch. Gen. Psychiatry, 48, 851-855. 2. Keller MB, Shapiro R, Lavori PW, et al, 1982 – Recovery in major depressione disorder: analysis with the life table and regression models. Arch. Gen. Psychiatry, 39, 905-910. 3. Angst J, 1992 – How reccurent and predictible is depressive illness? In: Montgomery S,Rouillon F. ed. Long-term treatment of depression. New York. Wiley. 4. Coryell W, Endicott J, Andreasen NC et. al, 1998 – Depression and panic attacks: the significance of overlap as reflected in follow-up and family study data. Am. J. Psychiatry,; 145, 293-300. 5. Keller MB, Mc Cullough JP, Klein DN et al., 2000 – A comparison of nefazodone, the cognitive behavioral-analysis system of psychotherapy, and their combination for the treatment of chronic depression. N. Engl. J. Med., 342, 1462-1480. 6. Pierre Schultz, 1999 – Are all antidepressants alike. Dialogues Clin. Scien., 1, 632-635. 7. Donald F. Klein, 1993 – False suffocation alarms, spontaneous panics, and related conditions. An integrative hypotesis. Arch. Gen. Psychiatry, 50, 306-317. 8. Kuhn Roland, 1957 – Über die Behandlung depressiver Zustände mit einem iminodibenzylderivat (G22355). Schweiz Med. Wohenschr., 87, 1135-1140. 9. Kendler KS, Karkowschi – Shuman L, 1997 – Stressful life events and generic liability to major depression: genetic control of exposure to the environment? Psychol. Med., 27, 359. 10. Kendler KS, 1997 – Social support: A genetic – epidemiological analysis. Am. J. Psychiatry, 154, 1398. 11. Akiskal HS, 1995 – Toward a temperament-based approach to depression: implications for neurobiologic research. Adv. Biochem. Psychopharmacol., 49, 99. 12. Klein Donald F, Fink Max, 1962 – Psychiatric reaction patterns to imipramine. Am. J. Psychiatry, 119, 432-438. 13. Bigger JTR, Giardina EG, Perel JM et. al, 1977 – Cardiac antiarrhytmic effect of imipramine hidrocloride. N. Engl. J. Med., 296, 206-208. 14. Post Robert, Weiss SRB, 1995 – The neurobiology of treatment resistent mood disorders. In Psychopharmacology: The Fourth Generation of Progress. FE Bloom, DJ Kupfer editors, Raven, New York. 15. Favis W A, 1958 – The history of Marsilid. J. clin .Exp. Psychopatol. Q.Rev. Psychiatry Neurol., 6, 1-10. 39

Bibliografie<br />

1. Frank E, Prien RF, Jarrett RB et al, 1991 – Conceptualization and rationale for consensus<br />

<strong>de</strong>finitions <strong>of</strong> terms in major <strong>de</strong>pressive disor<strong>de</strong>r: remission, recovery, relapse and<br />

recurrence. Arch. Gen. Psychiatry, 48, 851-855.<br />

2. Keller MB, Shapiro R, Lavori PW, et al, 1982 – Recovery in major <strong>de</strong>pressione disor<strong>de</strong>r:<br />

analysis with the life table and regression mo<strong>de</strong>ls. Arch. Gen. Psychiatry, 39, 905-910.<br />

3. Angst J, 1992 – How reccurent and predictible is <strong>de</strong>pressive illness? In: Montgomery<br />

S,Rouillon F. ed. Long-term treatment <strong>of</strong> <strong>de</strong>pression. New York. Wiley.<br />

4. Coryell W, Endicott J, Andreasen NC et. al, 1998 – Depression and panic attacks: the<br />

significance <strong>of</strong> overlap as reflected in follow-up and family study data. Am. J. Psychiatry,;<br />

145, 293-300.<br />

5. Keller MB, Mc Cullough JP, Klein DN et al., 2000 – A comparison <strong>of</strong> nefazodone, the<br />

cognitive behavioral-analysis system <strong>of</strong> psychotherapy, and their combination for the<br />

treatment <strong>of</strong> chronic <strong>de</strong>pression. N. Engl. J. Med., 342, 1462-1480.<br />

6. Pierre Schultz, 1999 – Are all anti<strong>de</strong>pressants alike. Dialogues Clin. Scien., 1, 632-635.<br />

7. Donald F. Klein, 1993 – False suffocation alarms, spontaneous panics, and related<br />

conditions. An integrative hypotesis. Arch. Gen. Psychiatry, 50, 306-317.<br />

8. Kuhn Roland, 1957 – Über die Behandlung <strong>de</strong>pressiver Zustän<strong>de</strong> mit einem<br />

iminodibenzyl<strong>de</strong>rivat (G22355). Schweiz Med. Wohenschr., 87, 1135-1140.<br />

9. Kendler KS, Karkowschi – Shuman L, 1997 – Stressful life events and generic liability to<br />

major <strong>de</strong>pression: genetic control <strong>of</strong> exposure to the environment? Psychol. Med., 27, 359.<br />

10. Kendler KS, 1997 – Social support: A genetic – epi<strong>de</strong>miological analysis. Am. J.<br />

Psychiatry, 154, 1398.<br />

11. Akiskal HS, 1995 – Toward a temperament-based approach to <strong>de</strong>pression: implications for<br />

neurobiologic research. Adv. Biochem. Psychopharmacol., 49, 99.<br />

12. Klein Donald F, Fink Max, 1962 – Psychiatric reaction patterns to imipramine. Am. J.<br />

Psychiatry, 119, 432-438.<br />

13. Bigger JTR, Giardina EG, Perel JM et. al, 1977 – Cardiac antiarrhytmic effect <strong>of</strong><br />

imipramine hidroclori<strong>de</strong>. N. Engl. J. Med., 296, 206-208.<br />

14. Post Robert, Weiss SRB, 1995 – The neurobiology <strong>of</strong> treatment resistent mood disor<strong>de</strong>rs. In<br />

Psychopharmacology: The Fourth Generation <strong>of</strong> Progress. FE Bloom, DJ Kupfer editors,<br />

Raven, New York.<br />

15. Favis W A, 1958 – The history <strong>of</strong> Marsilid. J. clin .Exp. Psychopatol. Q.Rev. Psychiatry<br />

Neurol., 6, 1-10.<br />

39

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