Paroxetine Dextromethorphan

D6 Bufuralol, bupranolol, clomipramine, clozapine, codeine, debrisoquin, dextromethorphan, encainide, flecainide, fluoxetine, guanoxan, haloperidol, hydrocodone, 4-methoxy-amphetamine, metoprolol, mexile-tine, oxycodone, paroxetine, phenformin, propafenone, propoxyphene, risperidone, selegiline (deprenyl), sparteine, thioridazine, timolol, tricyclic antidepressants Unknown Quinidine, paroxetine... 

D6 Desipramine, dextromethorphan, atomoxetine Paroxetine, quinidine, fluoxetine (use of PM vs. EM subjects) None identified... 

Timolol Desip ra mine Fluoxetine Fluvoxamine Imipramine Mianserin Nortriptyline Paroxetine Risperidone Thioridazine Zuclopenthixol Perhexiline Propafenone Sparteine Dextromethorphan Phenformin Tramadol... 

In 31 healthy men and women (mean age 28 years) the ability of four SSRIs (fluoxetine, fluvoxamine, paroxetine, and sertraline) to inhibit CYP2D6 activity was assessed in vivo, as judged by the dextromethorphan test (63). All were extensive metabolizers of dextromethorphan. After 8 days treatment at therapeutic doses, four of eight paroxetine-treated and five of eight fluoxetine-treated subjects had become poor metabolizers, presumably because of the inhibitory effect of the two SSRIs... 

CYP2D6 Antidepressants amitriptyline, clomipramine, imipramine, desipramine, nortriptyline, trimipramine, N-desmethyl-clomipramine, fluoxetine, norfluoxetine, paroxetine, venlafaxine, sertraline Neuroleptics chlorpromazine, thioridazine, perphenazine, haloperidol, reduced haloperidol, risperidone, clozapine, sertindole Others codeine, opiate, propranolol, dextromethorphan 4 no activity 25% in Caucasians 0%-10% in others 5 no activity 2%-10% in all groups 10 reduced activity 47%-70% in Asians <5% in others 17 reduced activity 25%-40% in blacks 0% in others 2XN increased activity 19%-29% in Arabs and Ethiopians <5% in others... 

Clinically important, potentially hazardous interactions with amitriptyline, amoxapine, clomipramine, desipramine, desvenlafaxine, dextromethorphan, doxepin, fluoxetine, fluvoxamine, imipramine, meperidine, nortriptyline, paroxetine, protriptyline, sertraline, sibutramine, trazodone, tricyclic antidepressants, trimipramine, venlafaxine... 

Clinically important, potentially hazardous interactions with amitriptyline, amoxapine, amphetamines, bupropion, citalopram, clomipramine, cyproheptadine, desipramine, dextroamphetamine, dextromethorphan, diethylpropion, dopamine, doxepin, entacapone, ephedra, ephedrine, epinephrine, fluoxetine, fluvoxamine, ginseng, imipramine, levodopa, mazindol, meperidine, methamphetamine, nefazodone, nortriptyline, paroxetine, phendimetrazine, phentermine, phenylephrine, pizotifen, propoxyphene, protriptyline, pseudoephedrine, rizatriptan, sertraline, sibutramine, sumatriptan, sympathomimetics, tramadol, tricyclic antidepressants, trimipramine, tryptophan, venlafaxine, zolmitriptan... 

Clinically important, potentially hazardous interactions with desvenlafaxine, dextromethorphan, dihydroergotamine, ephedra, ergot, fluoxetine, fluvoxamine, isocarboxazid, linezolid, lithium, MAO inhibitors, meperidine, methysergide, naratriptan, nefazodone, paroxetine, phenelzine, rizatriptan, sertraline, sumatriptan, tranylcypromine, tryptophan, venlafaxine, verapamil, zolmitriptan, zuclopenthixol... 

Whatever the precise mechanism, in vitro experiments with purified CYP2D6 indicate that the formation of MI complexes with a telltale spectroscopic signature at 456 nm may be responsible for the clinical reports of potent CYP2D6 inhibition by paroxetine (Figure 7.12), a serotonin reuptake inhibitor. The formation of a carbene complex is supported by the fact that paroxetine is metabolized by CYP2D6 via demethylenation of the methylenedioxy group to a catechol and formic acid - K, and t values of 6.6 2.7 p,M and 0.25 0.09 min , respectively, have been calculated for the paroxetine-mediated inhibition of human liver microsomal CYP2D6-dependent dextromethorphan O-demethylation-. ... 

D6 Debrisoquine 4-hydroxylation-[Pg.621]

CYP2C19 CYP2D6 diazepam, imipramine, 5-mephenytoin, omeprazol, proguanil, propranolol codeine, debrisoquine, dextromethorphan, flecainide, paroxetine, perphenazine, thioridazine carbamazepine, rifampicin cimetidine, felbamate fluoxetine, paroxetine, quinidine... 

B. lit addition, severe rigidity and hyperthermia may occur when patients receiving MAO inhibitors use therapeutic doses of meperidine (Demeroi), dextromethorphan, fluoxetine (Prozac), paroxetine (Paxii), sertraiine (Zoloft), ven-lafaxine (Effexor), or tryptophan the mechanism is unknown but may be related to inhibition of serotonin metabolism in the CNS, resulting in serotonin syndrome (see p 22). 

Three reports describe the development of a serotonin-like syndrome in two patients taking paroxetine and one taking citalo-pram and nefazodone, when they were given dextromethorphan. Another report describes hallucinations in a woman taking fluoxetine and dextromethorphan. 

The authors of this report very briefly deseribe another patient taking paroxetine who developed symptoms consistent with the serotonin syndrome within a few hours of taking a non-preseription eough remedy containing dextromethorphan and guaifenesin. She needed intensive care treatment. ... 

Not understood. The symptoms that developed with eitalopram or paroxetine and dextromethorphan were attributed by the authors of the reports to the serotonin syndrome, caused by the additive effeets of the SSRIs and dextromethorphan on serotonin transmission. It has also been suggested that paroxetine inhibited the cytochrome P450 isoenzyme CYP2D6, by which dextromethorphan is metabolised, resulting in increased dextromethorphan levels. Fluoxetine also inhibits CYP2D6. ... 

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