![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 284, Issue 1, 208-214, 1998
Department of Anesthesiology, University of Virginia Health
Sciences Center, Charlottesville, Virginia
Although tricyclic antidepressant (TCA) blockade of cardiac
Na+ channels is appreciated, actions on neuronal
Na+ channels are less clear. Therefore, the effects of TCAs
(amitriptyline, doxepin and desipramine) as well as trazadone and
fluoxetine on voltage-gated Na+ current (INa)
were examined in bovine adrenal chromaffin cells using the whole-cell
patch-clamp method. Amitriptyline produced concentration-dependent
depression of peak INa evoked from a holding potential of
80 mV with KD value of 20.2 µM and a Hill coefficient of 1.2. Although 20 µM amitriptyline
induced no change in the rate or voltage dependence of INa
activation, steady-state inactivation demonstrated a 15-mV
hyperpolarizing shift. Similar results were observed for doxepin and
desipramine. This shift in steady-state inactivation was associated
with a slowed rate of recovery from the inactivated state. Contrasting
results were observed with the atypical antidepressants: while 20 µM
fluoxetine depressed peak INa by 61% and caused a 7-mV
hyperpolarizing shift in steady-state inactivation, 100 µM trazodone
decreased peak INa by only 19% and caused only a 3-mV
shift. Although the magnitude of fluoxetine effects was similar to
those of the TCAs, the onset of fluoxetine effects was substantially
slower than for amitriptyline. In voltage-clamp and current-clamp
measurements from neonatal rat dorsal root ganglion neurons, 20 µM
amitriptyline decreased INa by 52% and depressed action
potential dynamics consistent with enhanced Na+ channel
inactivation. The effects of the TCAs on INa are similar to
local anesthetic behavior and could contribute to certain analgesic actions.
This article has been cited by other articles:
|
|
 |
|
  A. Ploppa, D. M. Ayers, T. Johannes, K. E. Unertl, and M. E. Durieux The Inhibition of Human Neutrophil Phagocytosis and Oxidative Burst by Tricyclic Antidepressants Anesth. Analg., October 1, 2008; 107(4): 1229 - 1235. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J P Mostert, F Admiraal-Behloul, J M Hoogduin, J Luyendijk, D J Heersema, M A van Buchem, and J De Keyser Effects of fluoxetine on disease activity in relapsing multiple sclerosis: a double-blind, placebo-controlled, exploratory study J. Neurol. Neurosurg. Psychiatry, September 1, 2008; 79(9): 1027 - 1031. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Lenkey, R. Karoly, J. P. Kiss, B. K. Szasz, E. S. Vizi, and A. Mike The Mechanism of Activity-Dependent Sodium Channel Inhibition by the Antidepressants Fluoxetine and Desipramine Mol. Pharmacol., December 1, 2006; 70(6): 2052 - 2063. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-Y. Choi, J. Li, S.-H. Jo, S.J. Lee, S.B. Oh, J.-S. Kim, J.-H. Lee, and K. Park Desipramine Inhibits Na+/H+ Exchanger in Human Submandibular Cells Journal of Dental Research, September 1, 2006; 85(9): 839 - 843. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Traboulsie, J. Chemin, E. Kupfer, J. Nargeot, and P. Lory T-Type Calcium Channels Are Inhibited by Fluoxetine and Its Metabolite Norfluoxetine Mol. Pharmacol., June 1, 2006; 69(6): 1963 - 1968. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Lirk, I. Haller, B. Hausott, S. Ingorokva, M. Deibl, P. Gerner, and L. Klimaschewski The Neurotoxic Effects of Amitriptyline Are Mediated by Apoptosis and are Effectively Blocked by Inhibition of Caspase Activity. Anesth. Analg., June 1, 2006; 102(6): 1728 - 1733. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. R. Benjamin, F. Pruthi, S. Olanrewaju, V. I. Ilyin, G. Crumley, E. Kutlina, K. J. Valenzano, and R. M. Woodward State-Dependent Compound Inhibition of Nav1.2 Sodium Channels Using the FLIPR Vm Dye: On-Target and Off-Target Effects of Diverse Pharmacological Agents J Biomol Screen, February 1, 2006; 11(1): 29 - 39. [Abstract] [PDF]
|
|
|
|
|
|
P. Gerner, V. Srinivasa, A. M. Zizza, Z.-Y. Zhuang, S. Luo, D. Zurakowski, S. Eappen, and G. Wang Doxepin by Topical Application and Intrathecal Route in Rats Anesth. Analg., January 1, 2006; 102(1): 283 - 287. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Oatway, A. Reid, and J. Sawynok Peripheral Antihyperalgesic and Analgesic Actions of Ketamine and Amitriptyline in a Model of Mild Thermal Injury in the Rat Anesth. Analg., July 1, 2003; 97(1): 168 - 173. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Haderer, P. Gerner, G. Kao, V. Srinivasa, and G. K. Wang Cutaneous Analgesia After Transdermal Application of Amitriptyline Versus Lidocaine in Rats Anesth. Analg., June 1, 2003; 96(6): 1707 - 1710. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. H. Sindrup, F. W. Bach, C. Madsen, L. F. Gram, and T. S. Jensen Venlafaxine versus imipramine in painful polyneuropathy: A randomized, controlled trial Neurology, April 22, 2003; 60(8): 1284 - 1289. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. N. Sengupta, B. K. Medda, and R. Shaker Effect of GABAB receptor agonist on distension-sensitive pelvic nerve afferent fibers innervating rat colon Am J Physiol Gastrointest Liver Physiol, December 1, 2002; 283(6): G1343 - G1351. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Thomas, B. Gut, G. Wendt-Nordahl, and J. Kiehn The Antidepressant Drug Fluoxetine Is an Inhibitor of Human Ether-A-Go-Go-Related Gene (HERG) Potassium Channels J. Pharmacol. Exp. Ther., February 1, 2002; 300(2): 543 - 548. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Nau, M. Seaver, S.-Y. Wang, and G. K. Wang Block of Human Heart hH1 Sodium Channels by Amitriptyline J. Pharmacol. Exp. Ther., March 1, 2000; 292(3): 1015 - 1023. [Abstract] [Full Text]
|
|
|
|
 |
|
 Z. Ungvari, P. Pacher, V. Kecskemeti, A. Koller, and E. P. Wei Fluoxetine Dilates Isolated Small Cerebral Arteries of Rats and Attenuates Constrictions to Serotonin, Norepinephrine, and a Voltage-Dependent Ca2+ Channel Opener • Editorial Comment Stroke, September 1, 1999; 30(9): 1949 - 1954. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
