Tetracyclic antidepressant

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Not to be confused with Tetracycline.
Chemical structure of the tetracyclic antidepressant mirtazapine. Notice its four fused rings.

Tetracyclic antidepressants (TeCAs) are a class of antidepressants that were first introduced in the 1970s. They are named after their chemical structure which contains four rings of atoms, and are closely related to the tricyclic antidepressants (TCAs), which contain three rings of atoms.

List of TeCAs[edit]

The TeCAs include the following agents:

Pharmacology[edit]

Binding profiles[edit]

The affinities (Kd (nM)) of a selection of TeCAs have been compared below at an assortment of binding sites:[1][2][3][4][5][6][7][8][9]

Compound SERT NET DAT 5-HT1A 5-HT2A α1 α2 D2 H1 mACh
Amoxapine 58 16.0 4,310 220 0.6 50 2,600 160 25 1,000
Loxapine 2,400 380 9,000 2,900 1.7 28 2,400 70 4.9 450
Maprotiline 5,800 11.1 1,000 12,000 120 91 9,400 350 2.0 560
Mianserin 4,000 101 9,400 190 4.3 74 4.3 2,197 1.7 820
Mirtazapine >100,000 1,640 >100,000  ? 69 500 19 >5,454 0.1 670
Oxaprotiline 3,900 4.9 4,340 67,000 2,400 620 42,000  ? 21 2,900

The selected ligands act as antagonists (or inverse agonists depending on the site in question) at all receptors listed and as inhibitors of all transporters listed.

References[edit]

  1. ^ Brunton, Laurence (2011). Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th Edition. China: McGraw-Hill. pp. 406–410. ISBN 978-0-07-162442-8. 
  2. ^ Tatsumi M, Groshan K, Blakely RD, Richelson E (December 1997). "Pharmacological profile of antidepressants and related compounds at human monoamine transporters". European Journal of Pharmacology 340 (2–3): 249–58. doi:10.1016/S0014-2999(97)01393-9. PMID 9537821. 
  3. ^ Wander TJ, Nelson A, Okazaki H, Richelson E (December 1986). "Antagonism by antidepressants of serotonin S1 and S2 receptors of normal human brain in vitro". European Journal of Pharmacology 132 (2–3): 115–21. doi:10.1016/0014-2999(86)90596-0. PMID 3816971. 
  4. ^ Richelson E, Nelson A (July 1984). "Antagonism by antidepressants of neurotransmitter receptors of normal human brain in vitro". The Journal of Pharmacology and Experimental Therapeutics 230 (1): 94–102. PMID 6086881. 
  5. ^ Tatsumi M, Jansen K, Blakely RD, Richelson E (March 1999). "Pharmacological profile of neuroleptics at human monoamine transporters". European Journal of Pharmacology 368 (2–3): 277–83. doi:10.1016/S0014-2999(99)00005-9. PMID 10193665. 
  6. ^ Wander TJ, Nelson A, Okazaki H, Richelson E (November 1987). "Antagonism by neuroleptics of serotonin 5-HT1A and 5-HT2 receptors of normal human brain in vitro". European Journal of Pharmacology 143 (2): 279–82. doi:10.1016/0014-2999(87)90544-9. PMID 2891550. 
  7. ^ Richelson E, Nelson A (August 1984). "Antagonism by neuroleptics of neurotransmitter receptors of normal human brain in vitro". European Journal of Pharmacology 103 (3–4): 197–204. doi:10.1016/0014-2999(84)90478-3. PMID 6149136. 
  8. ^ Fernández J, Alonso JM, Andrés JI, et al. (March 2005). "Discovery of new tetracyclic tetrahydrofuran derivatives as potential broad-spectrum psychotropic agents". Journal of Medicinal Chemistry 48 (6): 1709–12. doi:10.1021/jm049632c. PMID 15771415. 
  9. ^ de Boer TH, Maura G, Raiteri M, de Vos CJ, Wieringa J, Pinder RM (April 1988). "Neurochemical and autonomic pharmacological profiles of the 6-aza-analogue of mianserin, Org 3770 and its enantiomers". Neuropharmacology 27 (4): 399–408. doi:10.1016/0028-3908(88)90149-9. PMID 3419539.