Disease relevance of PENFLURIDOL

• Penfluridol patients had statistically fewer psychotic relapses [1].
• The low incidence of side effects and other signs of toxicity, coupled with an effective prophylactic activity, suggests that penfluridol is an important addition to our therapeutic armamentarium for the treatment of chronic schizophrenia [2].
• Although resting PRL levels were evaluated during initial penfluridol therapy (week 1), hypoglycemia provoked a further substantial PRL increment, not significantly different in magnitude from that induced by hypoglycemia during the drug-free period [3].
• A case of neuroleptic malignant syndrome (NMS) is discussed which occurred in a 72-year-old paranoid psychotic patient while on maintainance neuroleptic therapy with penfluridol [4].
• In rabbits tested for apomorphine-induced hyperthermia and gnawing, on the other hand, penfluridol blocks apomorphine for about a week [5].

Psychiatry related information on PENFLURIDOL

• Akathisia was more common with penfluridol but readily controlled with anti-parkinsonian medication [6].
• The bilateral application of dopamine into the nucleus accumbens of penfluridol-treated rats produced a very marked increase in coordinated locomotor activity which was 3-5 times higher than that of rats not treated with penfluridol [7].
• An open study was carried out in 17 acutely ill, newly admitted, floridly psychotic schizophrenic patients to a city hospital in New York. Penfluridol was given on a daily basis up to doses of 120 mg and patients were rated objectively by means of different psychometric evaluations; vital signs were monitored daily as were side effects [8].
• Changes in psychopathology in relation to EEG variables and visual averaged evoked responses (V.AER) in schizophrenic patients treated with penfluridol or thiothixene [9].
• Effects of penfluridol and other drugs on apomorphine-induced stereotyped behavior in monkeys [10].

High impact information on PENFLURIDOL

• Plasma prolactin and testosterone during penfluridol treatment [11].
• Plasma prolactin and testosterone during penfluridol treatment [12].
• Neuroleptic drugs attenuate calcium influx and tension development in rabbit thoracic aorta: effects of pimozide, penfluridol, chlorpromazine, and haloperidol [13].
• Sperm [Ca(2+)](i) increased upon incubation in high-pH or thimerosal-containing seawater, but only the high-pH-dependent elevation in [Ca(2+)](i) could be inhibited by pimozide or penfluridol [14].
• T-type Ca2+ channels in the human TT C cell line were blocked by penfluridol, and the potency was enhanced by reduction of extracellular Ca2+ [15].

Chemical compound and disease context of PENFLURIDOL

• Neuroleptic malignant syndrome due to combination of penfluridol and sulpiride [16]?

Biological context of PENFLURIDOL

• Penfluridol steady-state kinetics in psychiatric patients [17].
• When step depolarizations were applied at 0.1 Hz from a holding potential of -80 mV, with 10 mM Ca2+ as the charge carrier, the DPBP penfluridol inhibited T-type current with an IC50 of 224 nM [15].
• The model has been used to derive two possible binding sites for phenothiazines and one binding site for penfluridol [18].
• In mice given high-dose penfluridol apomorphine consistently elevates body temperatures, rather than exerts its usual hypothermic response [5].
• The major biotransformation pathways of penfluridol in the rat, rabbit, dog, and man were oxidative N-dealkylation followed by beta-oxidation, conjugation of penfluridol, and conjugation of the acidic metabolites [19].

Anatomical context of PENFLURIDOL

• The bilateral application of dopamine into the corpus striatum of penfluridol-treated animals produced a marked stereotyped behavioural syndrome in all rats studied, whereas no signs of stereotyped behaviour were observed in any of the rats not treated with penfluridol [7].
• The inhibition of IAC by DPBPs was selective because 200-fold higher concentrations of penfluridol were required to inhibit voltage-gated IA K+ channels in adrenal zona fasciculata cells [20].
• 2. Because of its unusual lipophilicity, penfluridol distributes extensively in fatty tissues following oral administration [21].
• 6. Lubeluzole (3 microM), R91154 (3 microM) and penfluridol (1 microM) blocked the current through Na+ channels in voltage-clamped chromaffin cells (I(Na)) by around 20-30% [22].
• The effect of penfluridol and some psychotropic drugs on monoamine metabolism in central nervous system [23].

Associations of PENFLURIDOL with other chemical compounds

• A long term comparative trial of penfluridol and fluphenazine decanoate in schizophrenic outpatients [24].
• Penfluridol, a compound with Ca2+-calmodulin-blocking properties, decreased control and A23187-stimulated cAMP content and PRL release [25].
• The coincubation of varying concentrations of penfluridol with 70 nM TRH, 50 mM K+, 3 mM (Bu)2cAMP, or 5 mM theophylline resulted in a dose-related inhibition of secretagogue-stimulated PRL secretion [26].
• Trifluoperazine and penfluridol were found to antagonize all the above mentioned types of activation of Ca2+-transport ATPase in the same concentration range [27].
• Furthermore, the penfluridol-induced increase of striatal DOPAC was more susceptible to reversal by apomorphine than was the increase of serum prolactin concentrations [28].

Gene context of PENFLURIDOL

• Inhibiting cAMP-dependent calmodulin with penfluridol had no effect on the initial spike phase, but reduced the sustained plateau phase of the response to AVP [29].
• In contrast cobalt, a calcium channel blocker, penfluridol, a calcium-binding protein inhibitor, and low-calcium medium decreased basal and TRH-induced prolactin release and diminished the TRH-induced release of arachidonate [30].
• The site of action of penfluridol may occur after calcium mobilization, with calmodulin a possible target for penfluridol's inhibitory action on PRL secretion [26].
• Preperifusion of the cells with 5 microM penfluridol, a calmodulin inhibitor, reduced CRF- and 8-Br-cAMP-induced ACTH release by 54% and 41%, respectively [31].
• In general, for the efficacy and safety measures, no differences were established, but penfluridol was superior in keeping the patients in treatment; 'leaving the study early' (n=218, 5RCTs, RR 0.55 CI 0.3 to 0.97, NNT 6 CI 3.4 to 50) [32].

Analytical, diagnostic and therapeutic context of PENFLURIDOL

• Fifty-nine patients participated in the initial dose titration segment during which doses of penfluridol were adjusted weekly until the patients' condition became stabilized [33].
• Fifty-six out of 60 schizophrenic patients completed a double-blind study of two long-acting neuroleptics, penfluridol (peroral) and flupenthixol decanoate (parenteral) [34].
• SELECTION CRITERIA: We reliably selected all randomised clinical trials comparing penfluridol to placebo or typical or atypical antipsychotic drugs for schizophrenia or serious mental illness [32].

References