Hostname: page-component-cd9895bd7-p9bg8 Total loading time: 0 Render date: 2024-12-25T18:06:39.939Z Has data issue: false hasContentIssue false
  • English
  • Français

Different modes of action of alprazolam in the treatment of panic attacks

Published online by Cambridge University Press:  18 September 2015

Dominique Van Gool
Get access Rights & Permissions [Opens in a new window]

Summary

Alprazolam (a benzodiazepine in the group of the triazolo-benzodiazepines) is a potent drug for the treatment of panic disorder. This is possible due to four different interactions with neurotransmitter systems. First, it facilitates, as all diazepines, the inhibitory acitivity of gamma-amino-butyricacid (GABA). The chemical structure differs from the benzodiazepines by incorporation of the triazoloring. Due to this triazoloring, the drug has three additional modes of action. These modes of action inhibit the locus coeruleus which plays a role in the origin of panic disorder. A first specific action is a stimulation of the serotonergic system. Triazolobenzodiazepines are also α2-adrenoreceptor agonists. Both mechanisms are responsible for inhibition of the locus coeruleus. Triazolo-benzodiazepines inhibit the platelet-activating-factor (PAF). PAF stimulates the corticotropin-releasing-hormone (CRH). This hormone stimulates the locus coeruleus. CRH in patients with panic attacks is elevated. This could be a result of hyperactive metabolism of the right parahippocampal area, which is observed in patients with panic attacks. Triazolo-benzodiazepines decrease the activity of the locus coeruleus because of a low CRH-level due to inhibited PAF.

Keywords

panicalprazolamlocus coeruleuscorticotro-pin-releasing-hormoneplatelet-activating-factor
Type
Articles
Information
Acta Neuropsychiatrica , Volume 12 , Issue 2 , June 2000 , pp. 41 - 45
Copyright
Copyright © Scandinavian College of Neuropsychopharmacology 2000

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Literatuur

1.Fawcett, JA, Kravitz, HM. Alprazolam: pharmacokinetics, clinical efficacy and mechanism of action. Pharmacotherapy 1982;2:243–254.Google Scholar
2.Dawson, GW, Jue, SG, Brogden, RN. Alprazolam. A review of its pharmacodynamic properties and efficacy in the treatment of anxiety and depression. Drugs 1984;27:132–147.Google Scholar
3.Overall, JE, Biggs, J, Jacobs, M, et al.Comparison of alprazolam and imipramine for treatment of outpatient depression. J Clin Psychiatry 1987;48:15–19.Google Scholar
4.Pecknold, J, Luthe, L, Munjack, D, Alexander, P. A double-blind, placebo controlled, multicenter study with Alprazolam and extended-release Alprazolam in the treatment of panic disorder. J Clin Psychopharmacol 1994;14:314–321.Google Scholar
5.Pollack, MH, Otto, MW, Tesar, GE, Cohen, LS, Meltzer-Brody, S, Rosenbaum, JF. Long-term outcome after acute treatment with Alprazolam or Clonazepam for panic disorder. J Clin Psychopharmacol 1993;13:257–263.Google Scholar
6.Tesar, GE, Rosenbaum, JF, Pollack, MH, Otto, MW, Sachs, GS, Herman, JB, Cohen, LS, Spier, SA. Double-blind, placebo-controlled comparison of clonazepam and alprazolam for panic disorder. J Clin Psychiatry 1990;51(suppl):4–10.Google Scholar
7.Kahn, RS, van Praag, HM. Panic disorder: a biological perspective. Eur Neuropsychopharmacol 1992;2:1–20.Google Scholar
8.Huybrechts, I. The pharmacology of Alprazolam; a review. Clin Ther 1991;13:100–117.Google Scholar
9.Albus, M, Lecrubier, Y, Maier, W, et al.Drug treatment of panic disorder: early response to treatment as a predictor of final outcome. Acta Psychiatr Scand 1990;82:359–365.Google Scholar
10.Mellergard, M, Lorentzen, K, Bech, P, et al.A trend analysis of changes during treatment of panic disorder with alprazolam and imipramine. Acta Psychiatr Scand 1991;365(suppl):28–32.Google Scholar
11.Leon, CA, De Arango, MV, Arevalo, W, et al.Comparacion del efecto del alprazolam, la imipramina y placebo en el tratamiento del trastorno de panico en Cali, Colombia. Acta Psiquiat Psicol Am Lat 1990;36:59–69.Google Scholar
12.Andersch, S, Rosenberg, NK, Kullingsjo, H, et al.Efficacy and safety of alprazolam, imipramine and placebo in treating panic disorder. A Scandinavian multicenter study. Acta Psychiatr Scand 1991;365 (suppl):18–27.Google Scholar
13.Clow, A, Glover, VSandler, M. Triazolam. An anomalous benzodiazepine receptor ligand: in vitro characterization of alprazolam and triazolam binding. J Neurochem 1985;45:621–625.Google Scholar
14.Sheehan, DV. Benzodiazepines in panic disorder and agoraphobia. J Affect Disord 1987;13:169–181.Google Scholar
15.Noyes, R, Garvey, MJ, Cook, BL. Benzodiazepines other than alprazolam in the treatment of panic disorder. In Ballanger, JC (ed). Clinical Aspects of Panic Disorder. London, Wiley-Liss, 1990, pp 251–258.Google Scholar
16.Van Gool, D, Igodt, P, De Cuyper, H. Mode of action of the triazolo-benzodiazepines in the treatment of panic attacks: a hypothesis. Eur Neuropsychopharmocol 1992;2:433–441.Google Scholar
17.Kornecki, E, Ehrlich, YH, Lenox, RH. Platelet-activating-factor-indu-ced aggregation of human platelets specially inhibited by triazolo-benzodiazepines. Science 1984;226:1454–1456.Google Scholar
18.Chesney, CM, Pifer, DD, Cagen, LM. Triazolobenzodiazepines competitively inhibit the binding of platelet activating factor (PAF) to human platelets. Biochem Biophys Res Commun 1987;144:359–366.Google Scholar
19.Kornecki, E, Lenox, RH, Hardwick, DH, et al.Interactions of the al-kyl-ether-phospholipid, platelet activating factor (PAF) with platelets, neural cells, and the psychotropic drugs triazolobenzodiazepines. Adv Exp Med Biol 1987;221:477–488.Google Scholar
20.Menkes, DB, Rasenick, MM, Wheeler, MA, et al.Guanosine triphosphate activation of brain adenylate cyclase: enhancement by long-term antidepressant treatment. Science 1983;219:65–67.Google Scholar
21.Bernardini, R, Calogero, AE, Ehrlich, YH, et al.The alkyl-ether phospholipid platelet-activating factor is a stimulator of the hypo-thalamic-pituitary-adrenal axis in the rat. Endocrinol 1989;125: 1067–1073.Google Scholar
22.Coryell, W, Noyes, R, Schlechte, J. The significance of HPA axis disturbance in panic disorder. Biol Psychiatry 1989;25:989–1002.Google Scholar
23.Goldstein, S, Halbreich, U, Asnis, G, et al.The hypothalamic-pituita-ry-adrenal system in panic disorder. Am J Psychiatry 1987;144:1320–1323.Google Scholar
24.Roy-Byrne, P, Uhde, TW, Post, RM, et al.The corticotropin-releasing hormone stimulation test in patients with panic disorder. Am J Psychiatry 1986;43:896–899.Google Scholar
25.Coryell, W, Noyes, R, Clancy, J, Crowe, R, Chaudhry, D. Abnormal escape from dexamethasone suppression in agoraphobia with panic attacks. Psychiatr Res 1985;15:301–311.Google Scholar
26.Coryell, W, Noyes, R. HPA axis disturbance and treatment outcome in panic disorder. Biol Psychiatry 1988;7:762–766.Google Scholar
27.Owens, MJ, Bissette, G, Nemeroff, CG. Acute effects of alprazolam and adinazolam on the concentrations of corticotropin-releasing factor in the rat brain. Synapse 1989;4:196–202.Google Scholar
28.Owens, MJ, Vargas, MA, Knight, DL, et al.The effects of alprazolam on corticotropin-releaseing factor neurons in the rat brain: acute time course, chronic treatment and abrupt withdrawal. J Pharmacol Exp Ther 1991;258:349–356.Google Scholar
29.Owens, MJ, Vargas, MA, Nemeroff, CB. The effects of alprazolam on corticotropin-releasing factor neurons in the rat brain: implications for a role for CRF in the pathogenesis of anxiety disorders. J Psychiatr Res 1993;27(suppl):209–220.CrossRefGoogle ScholarPubMed
30.Mellman, TA, Uhde, TW. Withdrawal syndrome with gradual tapering of alprazolam. Am J Psychiatry 1986;143:1464–1466.Google ScholarPubMed
31.Gold, PW. Possible role for corticotropin-releasing hormone in panic disorder. J Psychiatr Res 1990;24(suppl):86–87.Google Scholar
32.Eriksson, E, Carlsson, M, Nilsson, C, et al.Does alprazolam, in contrast to diazepam, activate alpha 2-adrenoreceptors involved in the regulation of rat growth hormone secretion? Life Sci 1986;38:1491–1498.Google Scholar
33.Rick-Brand, S, Müller, WE. Direct and indirect effects of alprazolam and Imipramine on α1 - and α2-adrenoreceptors in mouse forebrain. Pharmacopsychiatry 1988;21:319–320.Google Scholar
34.Uhde, TW, Stein, MB, Vittone, BJ, et al.Behavioral and physiologic effects of short-term and longterm administration of Clonidine in panic disorder. Arch Gen Psychiatry 1989;46:170–177.Google Scholar
35.TAirmel, A, De Montigny, C. Sensitization of rat forebrain neurons to serotonin by adinazolam, an antidepressant triazolo-benzodiazepi-ne. Eur J Pharmacol 1989;99:241–244.Google Scholar
36.Gray, JA. The neuropsychology of anxiety: an inquiry into the functions of the septo-hippocampal system. New York, Oxford University Press, 1988.Google Scholar
37.Swinson, RP, Kuch, K. Clinical features of panic and related disorders. In: Ballanger, JC (ed). Clinical Aspects of Panic Disorder. Willey-Liss, 1990, pp 11–30.Google Scholar
38.Ansseau, M. Critères de choix d'une benzodiazepine anxiolytique. Psiquiatria 1991;4:3–14Google Scholar
39.Timmerman, L. Biologische aspecten van paniekstoornis. Acta Neuropsychiatry 1994;6:6–11.Google Scholar
40.Gold, PW, Pigott, TA, Kling, MA, Brandt, HA, Kalogeras, K, Demitrack, MA, Geracioti, TD. Hypothalamic-pituitary-adrenal axis in panic disorder. In Ballanger, JC (ed). Neurobiology of Panic Disorder. Willey-Liss, 1990, pp 313–20.Google Scholar
41.Enna, SJ. Role of g-aminobutyric acid in anxiety. Psychopathology 1984;17(suppl): 15–24.Google Scholar
42.Paul, SM. Panic disorder: Pharmacology to molecular pathophysiology. Biol Psychiatry 1991;29(suppl):123.Google Scholar
43.Den Boer, JA, Westenberg, HGM. Krititsche kanttekeningen bij de locus coeruleus hypothese van paniekstoornis. Acta Neuropsychiatry 1993;5:48–54.Google Scholar
44.Charney, DS, Woods, SW, Price, LH, Goodman, WK, Glazer, WM, Henninger, GR. Noradrenergic dysregulation in panic disorder. In: Ballanger, JC (ed). Neurobiology of Panic Disorder. Willey-Liss, 1990, pp 91–105.Google Scholar
45.Gold, PW, Chrousos, G, Kellner, C, et al.Psychiatric implications of basal and clinical studies with corticotropin-releasing factor. Am J Psychiatry 1984;141:619–627.Google Scholar
46.Valentino, RJ, Foote, SL, Aston-Jones, G. CRF activates noradrenergic neurons of the locus ceruleus. Brain Res 1983;270:363–367.Google Scholar
47.Llinas, R. The intinsic electrophysiological properties of mammalian neurons: insights into central nervous system function. Science 1988;242:1654–1664.Google Scholar
48.Aghajanian, GK, Rogawski, MA. The physiological role of alpha-adrenoreceptors in the CNS: new concepts from single-cell studies. TIPS 1983;07:315–317.Google Scholar
49.Lingjaerde, O. Lactate induced panic attacs: possible involvement of serotonin reuptake stimulation. Acta Psychiatr Scand 1985;72:206–208.Google Scholar
50.Greene, RW, Haas, HL, Hermann, A. Effects of caffeine on hippo-campal pyramidal cells in vitro. Br J Pharmacol 1985;85:163–169.Google Scholar
51.Konnerth, A, Lux, HD, Morad, M. Proton-induced transformation of calcium channel in chick dorsal rooth ganglion cells. J Physiol 1987;386:603–633.Google Scholar
52.Aldenhoff, JB, Hennig, S. Corticosterone hyperpolarizes pyramidal neurons of the hippocampus in vitro. Soc Neurosci 1988;178:174.Google Scholar
53.Charney, DS, Heninger, GR. Noradrenergic function and the mechanism of action of antianxiety treatment, 2: the effect of long-term imipramine treatment. Arch Gen Psychiatry 1985;42:475–481.Google ScholarPubMed
54.Garfield, S, Gershon, S, Sletten, I. Chemically induced anxiety. Int J Neuropsychiatry 1967;3:426–433.Google Scholar
55.Woods, SW, Charney, DS, Loke, J, et al.Carbon dioxide sensitivity in panic anxiety. Arch Gen Psychiatry 1986;43:900–901.CrossRefGoogle ScholarPubMed
56.Woods, SW, Charney, DS, Goodman, WK, et al.Carbon dioxide-induced anxiety. Behavioral, physiologic, and biochemical effects of carbon dioxide in patients with panic disorders and healthy subjects. Arch Gen Psychiatry 1988;45:43–52.Google Scholar
57.Zemishlany, Z, McQueeney, R, Gabriel, SM, et al.Neuroendocrine and monoaminergic responses to acute administration of alprazolam in normal subjects. Neuropsychobiol 1990;23:124–128.Google Scholar
58.Sanghera, MK, McMillen, BA, German, DC. Buspirone. A non benzodiazepine anxiolytic, increases locus ceruleus noradrenergic neuronal activity. Eur J Pharmacol 1983;86:107–110.Google Scholar
59.Ludwig, CL, Weinberger, DR, Bruno, G. Buspirone. Parkinson's disease, and the locus ceuruleus. Clin Neuropharmacol 1986;9:373–378.Google Scholar
60.Kaitin, KI, Bliwise, DL, Gleason, C. Sleep disturbance produced by electrical stimulation of the locus ceruleus in a human subject. Biol Psychiatry 1986;21:710–716.Google Scholar
61.Den Boer, JA, Westenberg, HMG. Effect of a serotonin and a noradrenaline reuptake inhibitor in the panic disorder: a double-blind comparative study with fluvoxamine and maprotiline. Int Clin Psy-chopharmacol 1988;3:59–74.Google Scholar
62.Gorman, JM, Liebowitz, MR, Fyer, AJ, et al.An open trial of fluoxetine in the treatment of panic attacks. J Clin Psychopharmacol 1987;7:329–332.Google Scholar
63.Eriksson, E, Humble, M. Serotonin in psychiatric pathophysiology. In: Pohl, R, Gershon, S (eds). Progress in Basic and Clinical Pharmacology. Basel, Karger, 1990, pp 66–119.Google Scholar
64.Carr, DB, Sheehan, DV, Surman, OS, Coleman, JH, Greenblatt, DJ, Henigner, GR, Jones, KJ, Levine, PH, Watkins, WD. Neuroendocrine correlates of lactate-induced anxiety and their response to chronic alprazolam therapy. Am J Psychiatry 1986;143:483–494.Google Scholar
65.Cowley, DS, Dager, SR, Roy-Byrne, PP, et al. Lactate vulnerability after alprazolam versus placebo treatment of panic disorder. Biol Psychiatry 1991;30:49–56.Google Scholar
66.Gorman, JM, Askanazi, J, Liebowitz, MR, et al.Response to hyperventilation in a group of patients with panic disorder. Am J Psychiatry 1984;141:857–861.Google Scholar
67.Coryell, W. Hypersensitivity to carbon dioxide as a disease-specific trait marker. Biol Psychiatry 1997;41:259–263.Google Scholar
68.Reiman, EM, Raichle, ME, Butler, FK, et al.A focal brain abnormality in panic disorder. Nature 1984;310:683–985.Google Scholar
69.Reiman, EM, Raichle, ME, Robins, E, et al.The application of positron emission tomography to the study of panic disorder. Am J Psychiatry 1986;43:469–477.Google Scholar
70.Reiman, EM, Raichle, ME, Robins, E, et al.Neuroanatomical correlates of a lactate-induced anxiety attack. Arch Gen Psychiatry 1989;46:493–500.Google Scholar
71.Stewart, R, Devous, MD, Rush, AJ, et al.Cerebral blood flow changes during lactate induced panic attacks. Am J Psychiatry 1988;145:442–449.Google Scholar
72.Gorman, JM, Cohen, BS, Liebowitz, MR, et al.Blood gas changes and hypophosphatemia in lactate induced panic. Arch Gen Psychiatry 1986;43:1067–1071.Google Scholar