Nefazodone and the serotonin receptor modulators: a new member of a unique class of antidepressant agents

SummarySeveral new antidepressants have been introduced over the past 10 years with ever-differing mechanisms of action. The latest entry into clinical practice is nefazodone, a new member of a novel class of antidepressants known as serotonin receptor modulators (SRMs). SRMs have a pharmacological mechanism of action which distinguishes them from all other antidepressants, namely a dual mechanism of modulating serotonin receptors. SRMs specifically act by powerful and selective blockade of serotonin 2A receptors coupled with a lesser but necessary degree of serotonin uptake inhibition. This differs from the selective serotonin reuptake inhibitors (SSRIs) which only inhibit serotonin reuptake, and from the tricyclic antidepressants which also have undesirable blocking actions at alpha adrenergic, histaminergic and cholinergic receptors. The novel pharmacological actions of the SRM nefazodone suggest that its side effect profile differs significantly from other antidepressants, and that it may prove to hav...

[1]  L. D. van de Kar,et al.  Attenuation of hormone responses to the 5-HT1A agonist ipsapirone by long-term treatment with fluoxetine, but not desipramine, in male rats , 1994, Biological Psychiatry.

[2]  C. Clary,et al.  Nefazodone and Imipramine in Major Depression: A Placebo-Controlled Trial , 1994, British Journal of Psychiatry.

[3]  A. Ontiveros,et al.  A double-blind comparison of nefazodone, imipramine, and placebo in major depression. , 1994, The Journal of clinical psychiatry.

[4]  A. Rush,et al.  The Effects of Nefazodone on Sleep Architecture in Depression , 1994, Neuropsychopharmacology.

[5]  D. McTavish,et al.  Trazodone. A review of its pharmacology, therapeutic use in depression and therapeutic potential in other disorders. , 1994, Drugs & aging.

[6]  C. Cole,et al.  Characterization of the metabolites of the antidepressant drug nefazodone in human urine and plasma. , 1994, Drug metabolism and disposition: the biological fate of chemicals.

[7]  S. Dubovsky.  Beyond the serotonin reuptake inhibitors: rationales for the development of new serotonergic agents. , 1994, The Journal of clinical psychiatry.

[8]  N. Sussman.  The potential benefits of serotonin receptor-specific agents. , 1994, The Journal of clinical psychiatry.

[9]  J. Cummings,et al.  The neuroanatomy of depression. , 1993, The Journal of clinical psychiatry.

[10]  A. Bystritsky,et al.  Serotonergic (5-HT2) mediation of anxiety-therapeutic effects of serazepine in generalized anxiety disorder , 1993, Biological Psychiatry.

[11]  P. Cowen,et al.  Nefazodone—A novel antidepressant— May increase REM sleep , 1992, Biological Psychiatry.

[12]  S. Patten.  The comparative efficacy of trazodone and imipramine in the treatment of depression. , 1992, CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne.

[13]  P. Keck,et al.  Clozapine in the treatment of psychotic mood disorders, schizoaffective disorder, and schizophrenia. , 1991, The Journal of clinical psychiatry.

[14]  S. Marini,et al.  5‐HT2 receptor antagonism in dysthymic disorder: a double‐blind placebo‐controlled study with ritanserin , 1991, Acta psychiatrica Scandinavica.

[15]  R. Blashfield,et al.  Psychotropic medication and priapism: a comprehensive review. , 1990, The Journal of clinical psychiatry.

[16]  S. G. Bryant,et al.  A drug utilization review of prescribing patterns for trazodone versus amitriptyline. , 1990, Journal of Clinical Psychiatry.

[17]  S. Svebak,et al.  Clonazepam and imipramine in the treatment of panic attacks: a double-blind comparison of efficacy and side effects. , 1990, The Journal of clinical psychiatry.

[18]  C. de Montigny,et al.  A role for the serotonin system in the mechanism of action of antidepressant treatments: preclinical evidence. , 1990, The Journal of clinical psychiatry.

[19]  P. Cowen,et al.  L‐Tryptophan and prolactin release: Evidence for interaction between 5‐HT1 and 5‐HT2 receptors , 1986 .

[20]  E. Richelson,et al.  Antagonism by antidepressants of neurotransmitter receptors of normal human brain in vitro. , 1984, The Journal of pharmacology and experimental therapeutics.

[21]  D. Charney,et al.  Receptor sensitivity and the mechanism of action of antidepressant treatment. Implications for the etiology and therapy of depression. , 1981, Archives of general psychiatry.

[22]  D. Wong,et al.  Fluoxetine, a selective serotonin uptake inhibitor , 1978, Clinical pharmacology and therapeutics.

[23]  J. Schildkraut,et al.  The catecholamine hypothesis of affective disorders: a review of supporting evidence. , 1965, The American journal of psychiatry.

[24]  L. Johnson,et al.  Autonomic correlates of the photically activated EEG. , 1960, Journal of neuropsychiatry.

[25]  W. H. Wilson.  The Fifth Psychoactive Drug Usage Guide. , 1994, Journal of Clinical Psychiatry.

[26]  S. Stahl.  5HT1A receptors and pharmacotherapy. Is serotonin receptor down-regulation linked to the mechanism of action of antidepressant drugs? , 1994, Psychopharmacology bulletin.

[27]  E. Richelson,et al.  Blockade by newly-developed antidepressants of biogenic amine uptake into rat brain synaptosomes. , 1993, Life sciences.

[28]  E. Workman,et al.  Atypical antidepressants versus imipramine in the treatment of major depression: a meta-analysis. , 1993, The Journal of clinical psychiatry.

[29]  R. Fontaine.  NOVEL SEROTONERGIC MECHANISMS AND CLINICAL EXPERIENCE WITH NEFAZODONE , 1992, Clinical neuropharmacology.

[30]  A. S. Eison,et al.  Nefazodone: preclinical pharmacology of a new antidepressant. , 1990, Psychopharmacology bulletin.

[31]  D. Robinson,et al.  Placebo-controlled dose-ranging trial designs in phase II development of nefazodone. , 1990, Psychopharmacology bulletin.

[32]  J. Feighner,et al.  A comparison of nefazodone, imipramine, and placebo in patients with moderate to severe depression. , 1989, Psychopharmacology bulletin.

[33]  John W. Brazer.  Catecholamine hypothesis of affective disorders , 1969 .