| Toxicity |
Interacting Protein |
Mechanism |
Reference |
| Agranulocytosis | Myeloperoxidase precursor (P05164) | The oxidation of clozapine by the combination of myeloperoxidase to a reactive nitrenium ion that irreversibly binds to the cells@which could be responsible for clozapine-induced agranulocytosis. [ ADR Type 3 ] | Clozapine is oxidized by activated human neutrophils to a reactive nitrenium ion that irreversibly binds to the cells
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| Clinical Failure | Cytochrome P450 3A4 (P08684) | Clozapine inhibits CYP3A4 enzyme activity@thus decreases the plasma concentrations of tricyclic antidepressants@which may lead to clinical failure. [ ADR Type 4 ] | Clinical significance of pharmacokinetic interactions between antiepileptic and psychotropic drugs
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| Decreasing Clozapine Plasma Level | Cytochrome P450 1A2 (P05177) | Concomitant administration of drugs known to induce cytochrome P450 enzymes(CYP1A2@CYP2D6) may decrease the plasma levels of clozapine Phenytoin@ nicotine@ carbamazepine@ and rifampin may decrease FazaClo (clozapine@ USP) plasma levels resulting in a decrease in effectiveness of a previously effective FazaClo (clozapine@ USP) dose [ ADR Type 4 ] | Drug interactions with selective serotonin reuptake inhibitors, especially with other psychotropics
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| Increasing Clozapine Plasma Level | CYP2D6 (P10635) | Concomitant administration of drugs known to inhibit the activity of cytochrome P450 isozymes(CYP1A2@CYP2D6) may increase the plasma levels of clozapine Cimetidine@ caffeine@ fluvoxamine@ and erythromycin may increase plasma levels of FazaCloo (clozapine@ USP)@ potentially resulting in adverse effects Although concomitant use of FazaCloo (clozapine@ USP) and carbamazepine is not recommended@ it should be noted that discontinuation of concomitant carbamazepine administration may result in an increase in FazaCloo (clozapine@ USP) plasma levels [ ADR Type 4 ] | Comment: potential risk of valproic acid therapy in patients who are HIV-positive
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| Seizures | G protein-activated inward rectifier potassium channel (P48549) | Antipsychotic drugs also inhibited the cardiac-type GIRK1/4 heteromultimeric channels@underlies the side effect of seizures. [ ADR Type 1 ] | Inhibition by various antipsychotic drugs of the G-protein-activated inwardly rectifying K(+) (GIRK) channels expressed in xenopus oocytes
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| Side Effects Of Clozapine | delta-Type opioid receptor (P41143) | Effects of clozapine on the delta- and kappa-opioid receptors and the G-protein-activated K+ (GIRK) channel expressed in Xenopus oocytes@which suggests efficacy and side effects of clozapine under clinical conditions may be partly due to activation of the delta-opioid receptor and blockade of the GIRK channel [ ADR Type 1 ] | Effects of clozapine on the delta- and kappa-opioid receptors and the G-protein-activated K+ (GIRK) channel expressed in Xenopus oocytes
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| Side Effects Of Clozapine | G protein-activated inward rectifier potassium channel (P48549) | Effects of clozapine on the delta- and kappa-opioid receptors and the G-protein-activated K+ (GIRK) channel expressed in Xenopus oocytes@which suggests efficacy and side effects of clozapine under clinical conditions may be partly due to activation of the delta-opioid receptor and blockade of the GIRK channel [ ADR Type 1 ] | Effects of clozapine on the delta- and kappa-opioid receptors and the G-protein-activated K+ (GIRK) channel expressed in Xenopus oocytes
|
| Side Effects Of Clozapine | Kappa-Type opioid receptor (P41145) | Effects of clozapine on the delta- and kappa-opioid receptors and the G-protein-activated K+ (GIRK) channel expressed in Xenopus oocytes@which suggests efficacy and side effects of clozapine under clinical conditions may be partly due to activation of the delta-opioid receptor and blockade of the GIRK channel. [ ADR Type 1 ] | Effects of clozapine on the delta- and kappa-opioid receptors and the G-protein-activated K+ (GIRK) channel expressed in Xenopus oocytes
|
| Tachycardia | G protein-activated inward rectifier potassium channel (P48549) | In oocytes co-injected with GIRK1 and GIRK2 mRNAs@ application of thioridazine immediately caused a reduction of inward currents through the basally active GIRK channels@underlies the side effect of sinus tachycardia [ ADR Type 1 ] | Inhibition by various antipsychotic drugs of the G-protein-activated inwardly rectifying K(+) (GIRK) channels expressed in xenopus oocytes
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