Flupenthixole

Fluphenazine decanoate, Pipothiazine palmitate, FFaloperidol decanoate, Flupenthixol decanoate, Clopenthixol decanoate Psychosis... 

Across the sites, an average of 15% of inpatients received depot antipsychotic drugs (Sim etal, 2004b). This was most common in Singapore (75%) followed by Taiwan (20%), Japan and China (6%). The depot antipsychotic drugs used were fluphenazine decanoate, flupenthixol decanoate, zuclopenthixol decanoate, haloperidol decanoate, pipothiazine palmitate, and fluphenazine enanthate. 

The tranquillizers flupenthixol (353), clopenthixol (354), chlorprothixene (355) and thiothixene (356) showed batch-to-batch variation in their cisjtrans isomer ratio. 

Similar isomerizations of clopenthixol (354) and chlorprothixene (355) were observed but, unlike flupenthixol (353), the photostationary states of these mixtures differed significantly in their isomer ratios from those of the drugs as normally supplied. It was pointed out that the photoisomerizations could affect their potencies [195]. 

The pharmacological profiles of flupenthixol and zu-clopenthixol are similar to those of the piperazine-type phenothiazines. Patients with mild depression can have benefit from low dosages of flupenthixol. 

Quraishi S, David A. Depot flupenthixol decanoate for schizophrenia or other similar psychotic disorders. Cochrane Database Syst Rev 1999. Issue 4. 

Phenothiazines are also nonspecific dopaminergic antagonists and are an old family of neuroleptics. However, they are less and less used (fluphenazine, oxa-flumazine, trifluoperazine, triflupromazine). Flupenthixol and isofloxythepine are recent neuroleptics that can be grouped with phenothiazines (Figure 8.29). 

Fletcher A, Forster EA, Bill DJ, et al Electrophysiological, biochemical, neurohormonal and behavioural studies with WAY-100635, a potent, selective and silent 5-HTj receptor antagonist. Behav Brain Res 73 337-353, 1996 Fletcher PJ, Higgins GA Differential effects of ondansetron and alpha-flupenthixol on responding for conditioned reward. Psychopharmacology 134 64-72, 1997 Flood JF, Smith GE, Roberts E Dehydroepiandrosterone and its sulfate enhance memory retention in mice. Brain Res 447 269-277, 1988... 

Thioxanthenes lack the ring nitrogen of phenothiazine, and the side chain is attached by a double bond. In all cases, the cis isomer (relative to the substituted phenyl ring) is more active. Electron-attracting substituents seem to have a cumulative effect. For instance, pifluthixol (4.89), with a fluorine and a trifluoromethyl substituent, is 5-10 times more potent than its parent flupenthixol (4.90), and has an inhibitory effect (IC50 = 9.7 X 10 ° M) on the DA-sensitive adenylate cyclase of the striatum. 

Thioxanthene derivatives flupenthixol decanoate flupenthixol dihydrochloride thiothixene zuclopenthixol acetate zuclopenthixol decanoate zuclopenthixol dihydrochloride... 

The intramuscular administration of antipsychotics acting for weeks prevents this independent action and improves compliance on the other hand, only highly potent antipsychotics such as fluphenazine, flupenthixol and haloperidol are suitable for depot administration and it is precisely these medicines that lead more frequently to EPS and dysphoric mood (van Putten et al, 1984). 

One common denominator of all antipsychotics is the biockade of centrai dopamine (DA) receptors. As a result, extrapyramidal reactions, particularly parkinsonian symptoms, are a major adverse effect of many of these drugs, as well as an important clue to their mechanism of action. True Parkinson s disease is caused by a DA deficiency in the nigrostriatal system. Further, crystallographic data have demonstrated that CPZ s molecular configuration is similar to that of DA, which could explain its ability to block this neurotransmitter s receptors. Drugs with similar structures that do not block DA receptors (e.g., promethazine, imipramine) do not have antipsychotic activity. Another example is the isomer of flupenthixol, which blocks DA receptors is an effective antipsychotic, but the isomer that does not is ineffective (7). The other family of dopamine receptors, D and Dg, have not yet been implicated in psychosis. 

Johnson DAW, Ludlow JM, Street K, et ai. Double-blind comparison of half-dose and standard-dose flupenthixol decanoate in the maintenance treatment of stabilised outpatients with schizophrenia. Br J Psychiatry 1987 151 634-638. 

Wistedt B. A depot neuroleptic withdrawal study. A controlled study of the clinical effects of the withdrawal of depot fluphenazine decanoate and depot flupenthixol decanoate in chronic schizophrenic patients. Acta Psychiatr Scand 1981 64(l) 65-84. 

Flupenthixol and procyclidine Fluphenazine Prednisone and salbutamol Betal nut (Areca catechu) Rigidity, bradykinesia, jaw tremor Betal contains arecoline, a cholinergic alkaloid Tremor, stiffness, akithesia Inadequate control of asthma Arecoline challenge causes dose-related bronchoconstriction in patients with asthma... 

With the typical neuroleptics in wide clinical use (e.g. chlorpromazine, thioridazine, haloperidol, pimozide, flupenthixol and clopenthixol), there would appear to be a correlation between their D2 antagonistic potency and their clinical potency presumably the ability of these drugs to block 5-HT2 receptors to varying extents is also evidence that the serotonergic system is involved in their clinical activity in some way. 

The serum concentrations of "classical neuroleptics and their metabolites vary considerably in patients, even when the dose of drug administered has been standardized. Such interindividual variation may account for the differences in the therapeutic and side effects. High interindividual variations in the steady-state plasma levels have been reported for pimozide, fluphenazine, flupenthixol and haloperidol, some of these differences being attributed to differences in absorption and metabolism between patients. 

Augmentation - mood stabilizer, high potency first-generation neuroleptic (e.g. flupenthixol), possibly a benzodiazepine... 

---