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PubMed1976

[Experimental testing of a new gastrotherapeutic agent].

A new gastrotherapeutical preparation, AcT 72, has been evaluated. This preparation contains the anticholinergic drug propantheline bromide, the psychotherapeutical agent perazine, and antacids. In two different series of tests it was demonstrated that after a peroral dose of ACT72, gastric motility was significantly reduced when compared with the control situation. Dosages used were in accordance with normal therapeutic doses, and, because of the influence on gastric motility, the duration of action in the stomach was prolonged, thus reducing daily dose requirements. Reduction of stomach motility per se, has therapeutic value in patients with gastric ulcers.

Adult↗

PubMed1994

[Experiences of schizophrenic patients in ambulatory care with oral neuroleptics--baseline for psychoeducational interventions].

In the run-up to a prospective intervention study to assist the preparation of psychoeducational therapeutic measures, schizophrenic out-patients were questioned on their experiences with two oral neuroleptics, Clozapine and Perazine. The two drugs, which are known to have similar side effects, find equal acceptance among patients. Subjective attitudes to medication and general evaluations of drug therapy are extremely positive. Numerous patients had already modified their neuroleptic dosage on their own initiative, in most cases discontinuing their medication but in some cases increasing or reducing the dose. These experiences can be used in designing a psychoeducational intervention directed towards individual needs.

Adaptation, Psychological↗

PubMed2000

Determination of phenothiazines in human body fluids by solid-phase microextraction and liquid chromatography/tandem mass spectrometry.

Eleven phenothiazine derivatives with heavy side-chains were found to be extractable from human whole blood and urine samples by solid-phase microextraction (SPME) with a polyacrylate-coated fiber. The fiber was then injected into the desorption chamber of an SPME-liquid chromatography (LC) interface for LC/tandem mass spectrometry (MS/MS) with positive ion electrospray (ES) ionization. All compounds formed base peaks due to [M + 1](+) ions by LC/ES-MS/MS. By use of LC/ES-MS/MS, the product ions produced from each [M + 1](+) ion showed base peaks due to side-chain liberation. Selected reaction monitoring (SRM) and selected ion monitoring (SIM) were compared for the detection of the 11 phenothiazine derivatives from human whole blood and urine. SRM showed much higher sensitivity than SIM for both types of sample. Therefore, a detailed procedure for the detection of drugs by SRM with SPME-LC/MS/MS was established and carefully validated. The extraction efficiencies of the 11 phenothiazine derivatives spiked into whole blood and urine were 0. 0002-0.12 and 2.6-39.8%, respectively. The regression equations for the 11 phenothiazine derivatives showed excellent linearity with detection limits of 0.2-200 ng ml(-1) for whole blood and 4-22 pg ml(-1) for urine. The intra- and inter-day precisions for whole blood and urine samples were not greater than 15.1%. The data obtained after oral administration of perazine or flupentixol to a male subject are presented.

Adult↗

PubMed2004

Halogenation of drugs enhances membrane binding and permeation.

Halogenation of drugs is commonly used to enhance membrane binding and permeation. We quantify the effect of replacing a hydrogen residue by a chlorine or a trifluoromethyl residue in position C-2 of promazine, perazine, and perphenazine analogues. Moreover, we investigate the influence of the position (C-6 and C-7) of residue CF(3) in benzopyranols. The twelve drugs are characterized by surface activity measurements, which yield the cross-sectional area, the air-water partition coefficient, and the critical micelle concentration. By using the first two parameters (A(D) and K(aw)) and the appropriate membrane packing density, the lipid-water partition coefficients, are calculated in excellent agreement with the lipid-water partition coefficients measured by means of isothermal titration calorimetry for small unilamellar vesicles of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine. Replacement of a hydrogen residue by a chlorine and a trifluoromethyl residue enhances the free energy of partitioning into the lipid membrane, on average by deltaG(lw) approximately -1.3 or -4.5 kJ mol(-1), respectively, and the permeability coefficient by a factor of approximately 2 or approximately 9, respectively. Despite exhibiting practically identical hydrophobicities, the two benzopyranol analogues differ in their permeability coefficients by almost an order of magnitude; this is due to their different cross-sectional areas at the air-water and lipid-water interfaces.

Benzopyrans↗

PubMed2003

Screening, library-assisted identification and validated quantification of fifteen neuroleptics and three of their metabolites in plasma by liquid chromatography/mass spectrometry with atmospheric pressure chemical ionization.

A liquid chromatographic/mass spectrometric assay with atmospheric pressure chemical ionization (APCI-LC/MS) is presented for the fast and reliable screening and identification and for the precise and sensitive quantification of 15 neuroleptic (antipsychotic) drugs and three of their relevant metabolites in plasma. It allows confirmation of the diagnosis of a neuroleptic overdose and monitoring of psychiatric patients' compliance. The neuroleptics amisulpride, bromperidol, clozapine, droperidol, flupenthixol, fluphenazine, haloperidol, melperone, olanzapine, perazine, pimozide, risperidone, sulpiride, zotepine and zuclopenthixol and the pharmacologically active metabolites norclozapine, clozapine N-oxide and 9-hydroxyrisperidone were extracted from plasma using solid-phase extraction and were separated on a Merck LiChroCART column with Superspher 60 RP Select B as the stationary phase. Gradient elution was performed using aqueous ammonium formate and acetonitrile. After screening and identification in the scan mode using the authors' new LC/MS library, the neuroleptics were quantified in the selected-ion mode. The quantification assay was fully validated. It was found to be selective and proved to be linear from sub-therapeutic to over therapeutic concentrations for all analytes. The corresponding reference levels are listed. The accuracy and precision data were within the required limits. The analytes were stable in frozen plasma for at least 1 month. The method was successfully applied to several authentic plasma samples from patients treated or intoxicated with various neuroleptics. The validated LC/MS assay has proved to be appropriate for the isolation, separation, screening, identification and quantification of various neuroleptics in plasma for clinical toxicology and therapeutic drug monitoring purposes.

Antipsychotic Agents↗

PubMed1992

Pharmacokinetic interaction between carbamazepine and neuroleptics after combined prolonged treatment in rats.

This study investigates how neuroleptics of phenothiazine or thioxanthene structure influence the pharmacokinetics of carbamazepine. Experiments were carried out on male Wistar rats. Carbamazepine and the neuroleptics were administered i.p., separately or together, for 2 weeks in the following daily doses (mg/kg): carbamazepine 15 during the 1st week of treatment and 20 during the 2nd week of treatment, promazine 10, chlorpromazine 2, perazine 10, chlorprothixene 2, flupenthixol 0.5. One hour after the last injection of carbamazepine and/or the neuroleptic, samples of blood plasma and brain were taken to determine the concentrations of carbamazepine and two of its metabolites: 10,11-epoxide and trans-10,11-diol. The neuroleptics increased the concentration of carbamazepine in plasma and in brain, but tended to decrease (with the exception of chlorpromazine) the concentration of the epoxide and increased the concentration of trans-10,11-diol. Metabolic in vitro studies did not show any significant differences between rats treated with carbamazepine alone and those treated with carbamazepine plus neuroleptic in the rates of the carbamazepine epoxidation, of 10,11-epoxide hydrolysis or of 1-naphthol glucuronidation.

Animals↗

PubMed1988

Prediction of neuroleptic on-drug response in schizophrenic in-patients by EEG.

The subjects were 34 acutely ill in-patients who met the RDC criteria of schizophrenic psychosis, and 4 EEGs were recorded from each patient before, 2 h and 24 h after oral intake of a single dose of 150 mg perazine, and on the 28th day of the neuroleptic treatment period. As a criterion of clinical response a decrease of at least 66% in the schizophrenia-specific sum score of the Brief Psychiatric Rating Scale on day 28 relative to the baseline value was decided upon. The EEGs were assessed using a newly developed procedure which takes into consideration 4 derivations simultaneously. As we tried to search out EEG variables with predictive value the statistical data analysis underlying our findings should largely by regarded as exploratory. Independent of day, responders (R) showed a tendency towards more low voltage desynchronized epochs (non-A stage) than non-responders (NR). Thus, R exhibited a higher degree of dynamic variability or a broader range of control of the spontaneous vigilance fluctuation (dynamic lability) than NR (dynamic rigidity). Furthermore, R and NR differed with respect to their time-dependent changes of non-A epoch frequencies before medication. While R showed a monotonous increase which is typical for normals, NR did not. Because of considerable inter-individual variability these group differences could not be used for individual prediction of the therapy response. By means of a qualitative data analysis R could be distinguished from NR with regard to various test dose-induced changes of the topographical distribution of absolute alpha power. All the group differentiating variables showed a time course of the same kind: R showed a prompt and ample deflection and the same recovery of baseline; NR, in contrast, showed no significant deflections at all. These findings are in line with the results concerning the dynamics of vigilance and certain claims of earlier authors according to which EEG changeability should be decisive for therapeutic outcome.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

PubMed1992

Facial expression and emotional face recognition in schizophrenia and depression.

Twenty-three acute schizophrenics, 21 acute major depressives (Research Diagnostic Criteria), and 15 normal controls participated in a study on facial expression and emotional face recognition. Under clinical conditions, spontaneous facial expression was assessed according to the affective flattening section of the Scale for the Assessment of Negative Symptoms. Under experimental laboratory conditions involuntary (emotion-eliciting interview) and voluntary facial expression (imitation and simulation of six basic emotions) were recorded on videotape, from which a raterbased analysis of intensity or correctness of facial activity was obtained. Emotional face recognition was also assessed under experimental conditions using the same stimulus material. All subjects were assessed twice (within 4 weeks), controlling for change of the psychopathological status in the patient groups. In schizophrenics, neuroleptic drug influence was controlled by random allocation to treatment with either haloperidol or perazine. The main findings were that schizophrenics and depressives are characterized by different quantitative, qualitative, and temporal patterns of affect-related dysfunctions. In particular, schizophrenics demonstrated a trait-like deficit in affect recognition and in their spontaneous and voluntary facial activity, irrespective of medication, drug type and dosage, or extrapyramidal side-effects. In depressives a stable deficit could be demonstrated only in their involuntary expression under emotion-eliciting interview conditions, whereas in the postacute phase a reduction in their voluntary expression became apparent. Differences in patterns of affect-related behavioral deficits may reflect dysfunctions in different underlying psychobiological systems.

Adult↗

PubMed1996

An acute psychotic disorder caused by pefloxacin: a case report.

1. The patient, a 59 year old woman, developed a state of acute excitation several hours after the administration of 400 mg of the fluorquinolone pefloxacin in combination with 1000 mg paracetamol. Nine days later, after a total dosage of pefloxacin of 800 mg, she was admitted to our hospital with a psychotic disorder. 2. There was a full remission of symptoms after treatment with perazine up to a dosage of 500 mg/day. 3. Three years ago, the patient had developed a manic state under a medication with corticosteroids. 4. So far, the mechanism of--in this case--long-lasting central nervous side effects of fluorquinolones is not known. In patients with increased vulnerability of the CNS or in advanced age the application of fluorquinolones should be considered critically, in particular in combination with non-steroidal anti-inflammatory drugs.

Female↗

PubMed2005

Inhibition of rat liver CYP2D in vitro and after 1-day and long-term exposure to neuroleptics in vivo-possible involvement of different mechanisms.

The aim of the present study was to investigate the influence of classic and atypical neuroleptics on the activity of rat CYP2D measured as a rate of ethylmorphine O-deethylation. The reaction was studied in control liver microsomes in the presence of neuroleptics, as well as in microsomes of rats treated intraperitoneally (i.p.) for 1-day or 2-weeks (twice a day) with pharmacological doses of the drugs (promazine, levomepromazine, thioridazine, perazine 10 mg kg(-1); chlorpromazine 3 mg kg(-1); haloperidol 0.3 mg kg(-1); risperidone 0.1 mg kg(-1); sertindole 0.05 mg kg(-1)), in the absence of the neuroleptics in vitro. Neuroleptics added in vitro to control liver microsomes decreased the activity of the rat CYP2D by competitive or mixed inhibition of the enzyme. Thioridazine (Ki=15 microM) was the most potent inhibitor of the rat CYP2D among the drugs studied, whose effect was more pronounced than that of the other neuroleptics tested: phenothiazines (Ki=18-23 microM), haloperidol (Ki=32 microM), sertindole (Ki=51 microM) or risperidone (Ki=165 microM). The investigated neuroleptics-when given to rats in vivo-also seemed to exert an inhibitory effect on CYP2D via other mechanisms. One-day exposure of rats to the classic neuroleptics decreased the activity of CYP2D in rat liver microsomes. After chronic treatment with the investigated neuroleptics, the decreased CYP2D activity produced by the phenothiazines was still maintained, while that caused by haloperidol diminished. Moreover, risperidone decreased the activity of that enzyme. The obtained results indicate drug- and time-dependent interactions between the investigated neuroleptics and the CYP2D subfamily of rat cytochrome P-450, which may proceed via different mechanisms: (1) competitive or mixed inhibition of CYP2D shown in vitro, the inhibitory effects of phenothiazines being stronger than those of haloperidol or atypical neuroleptics, but weaker than the effects of the respective drugs on human CYP2D6; (2) in vivo inhibition of CYP2D, produced by both 1-day and chronic treatment with phenothiazines, which suggests inactivation of enzyme by intermediate metabolites; (3) in vivo inhibition of CYP2D by risperidone, produced only by chronic treatment with the drug, which suggests its influence on the enzyme regulation.

Animals↗

PubMed2006

Quantitative determination of forty-eight antidepressants and antipsychotics in human serum by HPLC tandem mass spectrometry: a multi-level, single-sample approach.

This method describes the simultaneous determination of amisulpride, amitriptyline, aripiprazole, benperidol, chlorpromazine, chlorprothixene, citalopram, clomipramine, clozapine, desipramine, doxepin, fluoxetine, flupentixol, fluphenazine, fluvoxamine, haloperidol, hydroxyrisperidone, imipramine, levomepromazine, maprotiline, mianserine, mirtazapine, moclobemide, norclomipramine, nordoxepin, norfluoxetine, nortriptyline, O-desmethylvenlafaxine, olanzapine, opipramol, paroxetine, perazine, perphenazine, pimozide, pipamperone, quetiapine, reboxetine, risperidone, sertraline, sulpiride, thioridazine, trazodone, trimipramine, venlafaxine, viloxazine, ziprasidone, zotepine and zuclopenthixol with a single sample/triple injection approach. Drugs were assigned to subgroups covering low, medium and high concentrations (overall range of therapeutic levels to be considered: 0.5-2000 ng/mL) by further dilution of the supernatant obtained after the first protein precipitation. Chromatographic separation was necessary for isobaric mass fragments and performed on a monolithic C18 column (50mmx4.6mm) with methanol gradient and 5mM acetate buffer at pH 3.9. The injection interval was 8 min. A set of three internal standards was used for quantification of drugs with widely varying hydrophobicity. After electrospray ionization positive ion fragments were detected in the multiple reaction monitoring (MRM) mode with an API 4000 tandem mass spectrometer. Regression parameters of calibration curves and limits of quantification showed good covering of therapeutic and subtherapeutic ranges with an average correlation coefficient of 0.9988. Imprecision and inaccuracy measures were prepared for intra- and inter-assay comparisons at three concentration ranges in all subgroups. Average coefficients of variation were 6.1% for intra-assay and 7.4% for inter-assay comparisons, while average deviations from spiked concentrations were 4.8% for intra-assay and 4.2% for inter-assay comparisons, respectively. Recovery rates, measured as the percent recoveries of spiked serum samples against standard solutions without serum matrix, varied between 92 and 111%, with an average of 101%. As the only exception, the olanzapine response was much higher (185%) in serum matrix than in matrix-free controls.

Antidepressive Agents↗

PubMed1998

p-Chloroamphetamine, a serotonin-releasing drug, elicited in rats a hyperglycemia mediated by the 5-HT1A and 5-HT2B/2C receptors.

The effects of a serotonin (5-HT) releasing drug, p-chloroamphetamine, on plasma glucose levels were investigated in rats. p-Chloroamphetamine elicited a significant hyperglycemia. The hyperglycemic effects of p-chloroamphetamine were completely prevented by the 5-HT synthesis inhibitor, p-chlorophenylalanine. Prior adrenodemedullation abolished the hyperglycemia elicited by p-chloroamphetamine. p-Chloroamphetamine-induced hyperglycemia was prevented by methysergide, which blocks the 5-HT1 and 5-HT2 receptor, the 5-HT1A/1B/2C receptor antagonist, (-)-propranolol, the selective 5-HT1A receptor antagonist, 4-(2'-methoxyphenyl-1-[2'-n-2"pyridinyl)-p-iodobenzamido]-ethyl-pi perazine (p-MPPI), the 5-HT2A/2B/2C receptor antagonists, ritanserin and 4-isopropyl-7-methyl-9-(2-hydroxy-1-methyl-propoxycarbonyl)-4,6A,7 ,8,9,10,10A-octahydro-indolo[4,3-FG]quinolone maleate(LY 53857). However, the 5-HT3 and 5-HT4 receptor antagonist, tropisetron, the 5-HT4 receptor antagonist, 2-methoxy-4-amino-5-chloro-benzoic acid 2-(diethylamino) ethyl ester (SDZ 205-557), and the 5-HT2A receptor antagonist, ketanserin, did not affect the p-chloroamphetamine-induced hyperglycemia. These results suggest that p-chloroamphetamine-induced hyperglycemia is elicited by an enhanced 5-HT release and facilitated adrenaline release. Moreover, our results indicate that p-chloroamphetamine-induced hyperglycemia is mediated by 5-HT1A and 5-HT2B/2C receptors.

4-Aminobenzoic Acid↗

PubMedDate not supplied

Prevalence of obesity in adolescent and young adult patients with and without schizophrenia and in relationship to antipsychotic medication.

The prevalence of obesity in inpatients of a German psychiatric rehabilitation center for adolescents and young adults (mean age 19.5 years) is assessed and set into relationship to diagnosis and medication regimen. In a cross-sectional naturalistic study body weights and heights of 151 inpatients, 109 of whom presented with ICD-10 schizophrenia spectrum disorders, were measured for the calculation of body mass indices (BMI, kg/m2); current medication regimen including the duration of treatment was assessed from medical records. BMIs were plotted into gender- and age-specific BMI-percentiles representative for the German population. Among the whole study population, obesity (BMI > or =90th percentile) was apparent in 44/98 (45%) of the male and in 31/53 (59%) of the female inpatients (overall: 50%). With respect to schizophrenia spectrum disorders, 36/70 (51%) males and 25/39 (64%) females (overall: 56%) were obese in contrast to 14/42 (33%) among the individuals without schizophrenia. Set into relationship to the treatment groups, the prevalence rates of obesity were 64% in patients treated with clozapine (n=69), 56% for other atypical antipsychotics (olanzapine, sulpiride, risperidone; n=27), 30% for classic antipsychotics (haloperidol, flupentixol, perazine; n=20) and 28% for the currently drug-free group (n=25). Together with other published findings in adults, these results suggest an increased prevalence of obesity among young patients with schizophrenia and especially among patients chronically treated with atypical antipsychotics.

Adolescent↗

PubMed2003

Mechanisms of cellular distribution of psychotropic drugs. Significance for drug action and interactions.

Distribution of a drug in the body is dependent on its permeation properties, the blood flow rates in various tissues, and on plasma and tissue uptake. The distribution of drugs in vivo is largely determined by uptake competitions between blood and tissues, as well as competitions among individual tissues. Basic lipophilic drugs are characterized by extensive accumulation in tissues, which leads to a high volume of distribution. Nonspecific binding to cellular membranes and uptake by acidic compartments (mainly lysosomes) are responsible for such a distribution pattern. Lysosomal trapping is an important mechanism of distribution of basic psychotropic drugs; however, the tissue distribution of the aliphatic-type phenothiazine neuroleptic promazine, tricyclic antidepressants (TADs) and selective serotonin reuptake inhibitors (SSRIs) depends more on phospholipid binding than on lysosomal trapping, whereas in the case thioridazine and perazine, lysosomal trapping is as important for the tissue uptake as is phospholipid binding. Neuroleptics and antidepressants mutually inhibit their lysosomal uptake. A decrease in the intralysosomal drug concentrations in vivo leads to a shift of the drug from organs abundant in lysosomes (lungs, liver and kidneys) to those poor in these organella, e.g., the heart, which may be of clinical importance (cardiotoxicity). The brain is not a homogenous organ, i.e., the phospholipid pattern and density of lysosomes vary in its different regions. Therefore, the contribution of the two mechanisms (lysosomal trapping and tissue binding) to total drug uptake is different in areas of the brain. Both lysosomal trapping and binding to cellular elements for psychotropics are higher in the grey matter and neurons than in the white matter and astrocytes, respectively. Lysosomal trapping and distribution interactions of psychotropics take place mainly in neurons. A decrease (via a distributive interaction) in the concentration of psychotropics in lysosomes (depot) may lead to an increase in their level in membranes and tissue fluids (i.e., in concentrations and compartments relevant to their pharmacological action) and, in consequence, to enhancement of the drug binding to neurotransmitter receptors and/or transporters.

Antidepressive Agents↗

PubMed2000

The hypothalamic-pituitary-thyroid axis in patients with schizophrenia.

Serum concentrations of thyroxine (T(4)), triiodothyronine (T(3)), reverse triiodothyronine (rT(3)) and thyrotropine (TSH) were measured in 31 acutely ill in-patients with schizophrenia before and after four weeks of treatment with the phenothiazine derivative perazine. The serum levels of all the above hormones were also determined in 19 schizophrenic patients in remission who were receiving no medication, 20 schizophrenic patients in remission taking neuroleptic drugs, and 24 patients with residual-type schizophrenia. The serum levels of T(4) of acutely ill schizophrenic patients were elevated, while those of T(3), rT(3) and TSH were normal. Their T(4) levels showed a positive correlation with the severity of illness and the degree of clinical response to neuroleptic treatment. There was a significant fall in serum concentrations of T(4) and rT(3) during four weeks of drug treatment and the decrease was significantly correlated to clinical response. No abnormalities in the serum concentrations of any of the hormones measured were found in schizophrenic patients in remission or in residual-type schizophrenia. In conclusion, our results indicate that the elevated serum levels of T(4) may be specific for acutely ill schizophrenic patients and that neuroleptic medication may affect thyroid hormone metabolism, this interaction being involved in the mechanism of action of these drugs.

Acute Disease↗

PubMed2003

Which neuroleptic would psychiatrists take for themselves or their relatives?

OBJECTIVE: Psychiatrists should be asked which neuroleptic they would prefer for themselves and their relatives in the case of first manifestation of schizophrenia. METHOD: Questionnaires were answered by 66 psychiatrists from 13 different sites in Baden-Wuerttemberg (South West Germany). Only those were included who had treated more than 50 patients with schizophrenia within the last 5 years (n = 54). RESULTS: The psychiatrists were experienced with conventional and most of the atypical agents. Fifty-one point nine percent would take olanzapine as first line treatment, 20.4% risperidone, 13.0% quetiapine, 9.3% amisulpride, 3.7% haloperidol and 1.9% perazine. In four cases, different substances were preferred for oneself and relatives. CONCLUSION: Most psychiatrists would not take conventional neuroleptics, though 70% of prescriptions for schizophrenic patients have been conventional neuroleptics in Germany in 2000. The preferences among atypicals correspond well with the current prescription practice in Germany.

Adult↗

PubMed1998

Effects of antagonists at the human recombinant P2X7 receptor.

1. We have used whole-cell patch clamping methods to examine the properties of the recombinant human P2X7 (P2Z) receptor stably expressed in HEK-293 cells. 2. In an extracellular solution with lowered concentrations of divalent cations (zero Mg2+ and 0.5 mM Ca2+), both ATP and the nucleotide analogue, 2'- and 3'-O-(4-benzoylbenzoyl)-adenosine 5'-triphosphate (Bz-ATP) evoked concentration-dependent whole-cell inward currents with maxima of 4658+/-671 and 5385+/-990 pA, respectively, at a holding potential of -90 mV. Current-voltage relationships determined using 100 microM Bz-ATP reversed at -2.7+/-3.1 mV, and did not display significant rectification. 3. Repeated applications of 300 microM Bz-ATP produced inward currents with similar rise-times (approx. 450 ms, 5-95% current development) but with progressively slower 95-5% decay times, with the eighth application of this agonist yielding a decay time of 197% of the first application. 4. Concentration-effect curves to ATP and Bz-ATP produced estimated EC50 values of 780 and 52.4 microM, respectively. Consecutive concentration-effect curves to Bz-ATP produced curves with similar maxima and EC50 values. 5. The non-selective P2 antagonists, pyridoxal-phosphate-6-azophenyl-, 2',4'-disulphonic acid (PPADS) and suramin, both produced concentration-dependent increases in maximal inward currents to Bz-ATP, with IC50 concentrations of approximately 1 microM and 70 microM, respectively. The profile of antagonism produced by PPADS was not that of a competitive antagonist. 6. The isoquinolene derivatives 1-(N,O-bis[5-isoquinolinesulphonyl]-N-methyl-L-tyrosyl)-4-phenylpi perazine (KN-62) and calmidazolium both produced antagonism which was not competitive, with IC50 concentrations of approximately 15 and 100 nM, respectively. HMA (5-(N,N-hexamethylene)- amiloride) was also an effective antagonist at a concentration of 10 microM. The group IIb metal, copper, also displayed antagonist properties at the human P2X7 receptor, reducing the maximum response to Bz-ATP by about 50% at a concentration of 1 microM. 7. These data demonstrate that the human recombinant P2X7 receptor displays functional behaviour which is similar to the recombinant rat P2X7 receptor, but has a distinct pharmacological profile with respect to agonist and antagonist sensitivity.

Adenosine Triphosphate↗

PubMed1999

An HPLC assay for the determination of ketoconazole in common pharmaceutical preparations.

An HPLC method is described using octadecylsilica (3 microns) with an acetonitrile phosphate buffer mobile phase containing diethylamine which is capable of separating ketoconazole [(+/-)-cis-1-acetyl-4-(4[2-(dichlorophenyl)-2- (1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl)pi perazine] from four related compounds, (R049223, R063600, R053165 and R039519) and from excipients in tablets, cream and shampoo. The method was validated using an external calibration method for tablets, shampoo and creams and a standard addition method for cream. The limits of detection for the related compounds in the presence of ketoconazole are also reported.

Antifungal Agents↗