Clozapin

Many examples of retention of activity in the face of replacement of benzene by thiophene have been noted so far. Application of this stratagem to a clozapine-like antipsychotic constitutes yet another example where activity is retained. The seven-membered ring of the compound in question is established by intramolecular amide formation on intermediate 102. Treatment of amide 103 with N-methylpiperazine in the presence of titanium tetrachloride affords flumezapine (104) [20]. 

The breadth of the SAR in the clozapine series is demonstrated by the fact that antipsychotic activity is retained when the dibcnzdiazcpinc nucleus of the parent molecule is replaced by an imidazobenzothiadiazepine ring system which contains twice as many hetero atoms. Preparation... 

O. V. Olesen and B. Poulsen, On-line fully automated deteimination of clozapine and desmethylclozapine in human semm by solid-phase extraction on exchangeable car-ti idges and liquid cliromatography using a methanol buffer mobile phase on unmodified silica , 7. Chromatogr. 622 39-46 (1993). 

Youngren KD, Inglis FM, Pivirotto PJ et al (1999) Clozapine preferentially increases dopamine release in the rhesus monkey prefrontal cortex compared with the caudate nucleus. Neuropsychopharmacology 20 403-12... 

Neuroleptics or antipsychotics suppress the positive symptoms of schizophrenia such as combativeness, hallucinations and formal thought disorder. Some also alleviate the negative symptoms such as affective blunting, withdrawal and seclusiveness. Neuroleptics also produce a state of apathy and emotional indifference. Most neuroleptics block dopamine D2-receptors but some, like clozapine, also block dopamine D4-receptors or serotonin 5-hydroxytryptamine2A-receptors. 

Antipsychotic drug s are classified as Pregnancy Category C dm (except for clozapine which is Pregnancy Category B). Safe use of these dragp during... 

Note that only a 1-week supply of clozapine is dispensed at a time. The drug is obtained through a special program designed to ensure the required blood monitoring. Weekly WBC laboratory tests are required. Immediately report any signs of weakness, fever, sore throat, malaise, or flu-like symptoms to the primary care provider. 

Your patient is prescribed clozapine for schizophrenia that has not responded to other drugs. You must discuss this new therapy with the family. Discuss what points to include in this family teaching session. 

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