Disease relevance of Desyrel

• Treatment of painful diabetic neuropathy with trazodone [1].
• Trazodone in essential tremor [2].
• Trazodone associated with priapism [3].
• Trazodone and liver toxicity [4].
• Chronic active hepatitis associated with trazodone therapy [5].

Psychiatry related information on Desyrel

• Trazodone treatment of obsessive-compulsive disorder and trichotillomania [6].
• Increased libido with trazodone [7].
• Trazodone in the treatment of panic disorder and agoraphobia with panic attacks [8].
• Trazodone-induced mania following desipramine-induced mania in major depressive disorders [9].
• Effects of trazodone on aggressive behavior in seven patients with organic mental disorders [10].

High impact information on Desyrel

• The physiologic and subjective effects of an oral 2-mg/kg dose of cocaine hydrochloride were measured in eight healthy cocaine-using men after pretreatment with a single, 100-mg oral dose of the triazolopyridine antidepressant trazodone hydrochloride or placebo in a double-blind study [11].
• Trazodone and intrahepatic cholestasis [12].
• Sleep apnea in olivopontocerebellar degeneration: treatment with trazodone [13].
• Agranulocytosis probably induced by trazodone [14].
• Trazodone induction of migraine headache through mCPP [15].

Chemical compound and disease context of Desyrel

• Meta-Chlorophenylpiperazine (m-CPP), a serotonin agonist and metabolite of the anti-depressant trazodone, was administered chronically to eight moderate to severely affected Alzheimer patients to determine whether it would produce improvement in behavioral symptoms complicating this illness [16].
• All patients suffered hemispheric ACI, were seen within 24 hours of onset, and were treated with low dose, subcutaneous heparin to prevent venous thrombosis; 25 received 10 mg. of trazodone hydrochloride intravenously every 12 hours for seven days and 24 were given an identically appearing placebo [17].
• The effects of trazodone with L-tryptophan on sleep-disordered breathing in the English bulldog [18].
• Interactions of trazodone with the azole antifungal agent, ketoconazole, and with human immunodeficiency virus protease inhibitors (HIVPIs) were studied in the same system [19].
• Treatment of the sleep apnea with nasal continuous positive airway pressure (CPAP), protriptyline, trazodone, acetazolamide, or tracheostomy reduced seizure frequency and severity in six patients [20].

Biological context of Desyrel

• High (17 nM) and low (603 nM) affinity binding sites for [3H]tetrahydrotrazodone ([3H] THT), a biologically active analogue of trazodone, have been identified in rat brain membranes [21].
• Absolute bioavailability of oral trazodone averaged 70% to 90% and was unrelated to age or sex [22].
• Trazodone kinetics: effect of age, gender, and obesity [22].
• METHODS: Biotransformation of the antidepressant trazodone to its principal metabolite, meta-chlorophenylpiperazine (mCPP), was studied in vitro using human liver microsomes and heterologously expressed individual human cytochromes [19].
• The 3- to 9-hour half-life of trazodone and its pharmacokinetics favors a dose weighted at bedtime [23].

Anatomical context of Desyrel

• RESULTS: Formation of mCPP from trazodone in liver microsomes had a mean (+/- SE) K(m) value of 163 (+/- 21) micromol/L [19].
• Among heterologously expressed human cytochromes, only CYP3A4 mediated formation of mCPP from trazodone; the K(m) was 180 micromol/L, consistent with the value in microsomes [19].
• Trazodone, its active metabolite 1-(m-chlorophenyl)piperazine (mCPP) and two isomers of mCPP were tested for affinity to the binding sites for [3H]flunitrazepam ([3H]FLU) and [3H]p-aminoclonidine ([3H]pAC) in the frontal cortex, amygdala and hippocampus of the rat [24].
• Comparative effects of trazodone and tricyclic antidepressants on uptake of selected neurotransmitters by isolated rat brain synaptosomes [25].
• Intracavernosal trazodone results in erectile activity that appears in part based on its local alpha blocking activity but like other intracavernosal alpha-blocking agents is not as effective in initiating penile erections as are intracavernosal agents that directly induce smooth muscle relaxation [26].

Associations of Desyrel with other chemical compounds

• Indol derivatives were consistently higher in the spinal fluid of trazodone patients after treatment, confirming serotonin reuptake blockage; however, this seems to have had no beneficial effect on the outcome of ACI [17].
• OBJECTIVE: To compare haloperidol, trazodone, and BMT with placebo in the treatment of agitation in AD outpatients [27].
• We therefore performed multitrials/dose, multidose, randomized sleep studies testing the effectiveness of a combination of serotoninergics, trazodone, and L-tryptophan, in our animal model of OSAHS, the English bulldog [18].
• In vitro metabolism of trazodone by CYP3A: inhibition by ketoconazole and human immunodeficiency viral protease inhibitors [19].
• A comparative trial of fluoxetine versus trazodone in outpatients with major depression [28].

Gene context of Desyrel

• This study was carried out to examine the effects of clomipramine, sertraline, and trazodone on the stimulated production of IFN gamma, a pro-inflammatory cytokine, and IL-10, a negative immunoregulatory cytokine [29].
• The present results indicate that trazodone is a substrate for CYP3A4, that CYP3A4 is a major isoform involved in the production of mCPP from trazodone, and that there is the possibility of drug-drug interactions with trazodone and other substrates, inducers and/or inhibitors of CYP3A4 [30].
• The kinetics of mCPP formation from trazodone were determined, and three in vitro experiments were performed to identify the major P450 enzyme involved [30].
• Furthermore, at 5, 10 and 20 mg/kg, trazodone blocks 5-HT 2A and 5-HT 2C receptors [31].
• Relationship between the CYP2D6 genotype and the steady-state plasma concentrations of trazodone and its active metabolite m-chlorophenylpiperazine [32].

Analytical, diagnostic and therapeutic context of Desyrel

• To monitor trazodone effect, indol derivatives were measured in spinal fluid collected before and after treatment in 38 patients [17].
• Fifteen healthy adults, aged 60 years and older, participated in a double-blind, crossover study of trazodone in comparison with amitriptyline and placebo [33].
• Steady-state plasma levels of trazodone were determined by HPLC in 11 elderly depressed patients who underwent a 5-week pharmacological treatment with 150 mg/day trazodone in three oral administrations [34].
• ECG findings in geriatric depressives given trazodone, placebo, or imipramine [35].
• Trazodone and hemodialysis [36].

References