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At least 451 records · Page 25Linked to original sources
PubMed2006

Antipsychotic drugs inhibit the human corticotropin-releasing-hormone gene promoter activity in neuro-2A cells-an involvement of protein kinases.

Antipsychotic drugs can regulate transcription of some genes, including those involved in regulation of hypothalamic-pituitary-adrenal (HPA) axis, whose activity is frequently disturbed in schizophrenic patients. However, molecular mechanism of antipsychotic drug action on the corticotropin-releasing hormone (CRH) gene activity has not been investigated so far. This study was undertaken to examine the influence of conventional and atypical antipsychotic drugs on the CRH gene promoter activity in differentiated Neuro-2A cell cultures stably transfected with a human CRH promoter fragment linked to the chloramphenicol acetyltransferase (CAT) reporter gene. It has been found that chlorpromazine (0.1-5.0 microM), haloperidol (0.5-5.0 microM), clozapine (1.0-5.0 microM), thioridazine (1.0-5.0 microM), promazine (5.0 and 10 microM), risperidone (5.0 and 10.0 microM), and raclopride (only at the highest used concentrations, ie 30 and 100 microM) present in culture medium for 5 days inhibited the CRH-CAT activity. Sulpiride and remoxipride had no effect. Since CRH gene activity is most potently enhanced by cAMP/protein kinase A pathway, the effect of antipsychotics on the forskolin-induced CRH-CAT activity was determined. Chlorpromazine (1.0-5.0 microM), haloperidol (1.0-5.0 microM), clozapine (1.0-5.0 microM), thioridazine (3.0 and 5.0 microM), and raclopride (30 and 100 microM), but not promazine, sulpiride, risperidone, and remoxipride, inhibited the forskolin-stimulated CRH gene promoter activity. A possible involvement of protein kinases in chlorpromazine and clozapine inhibitory action on CRH activity was also investigated. It was found that wortmannin (0.01 and 0.02 microM), an inhibitor of phosphatidylinositol 3-kinase (PI3-K), significantly attenuated the inhibitory effect of chlorpromazine and clozapine on CRH gene promoter activity. In line with these results, a Western blot study showed that these drugs increased phospho-Ser-473 Akt level, had no effect on total Akt, and decreased glycogen synthase kinase-3beta level. Additionally, we found that clozapine decreased protein kinase C (PKC) level and that its action on CRH activity was attenuated by PKC activator (TPA, 0.1 microM). The obtained results indicate that inhibition of CRH gene promoter activity by some antipsychotic drugs may be a molecular mechanism responsible for their inhibitory action on HPA axis activity. Clozapine and chlorpromazine action on CRH activity operates mainly through activation of the PI3-K/Akt pathway. Moreover, PKC-mediated pathway seems to be involved in clozapine action on CRH gene activity.

Antipsychotic Agents↗
PubMed1999

Analysis of tricyclic antidepressants using electrogenerated chemiluminescence.

A novel method has been investigated for the selective and sensitive determination of a range of tricyclic antidepressants including amitriptyline, doxepin, nortriptyline, promazine, chlorpromazine, imipramine, clomipramine, desipramine, protriptyline and trimipramine using electrogenerated chemiluminescence (ECL). The ECL mechanism is based on the reaction between tris(2,2'-bipyridyl)ruthenium(II) [Ru(bpy)3(2+)] and the tertiary amino groups on the antidepressants. After selecting the best operating parameters calibration curves were obtained over three orders of magnitude for amitriptyline, doxepin, nortriptyline, promazine and chlorpromazine. Linear calibrations were used to obtain limits of detection in the range 0.09-0.24 microgram ml-1 with relative standard deviations below 4% for five replicate samples. Rapid depression in the signal was observed with repeat analysis of imipramine, clomipramine, protriptyline, desipramine and trimipramine due to electrode fouling by the oxidation product of the reaction. Use of a lower concentration of the compound was found to alleviate the problem. Finally the concentration of doxepin was determined in a pharmaceutical preparation.

Antidepressive Agents, Tricyclic↗
PubMed1983

The diagnostic value of the sleep EEG with and without sleep deprivation in patients with atypical absences.

Hitherto it has not been known whether or not the sleep EEG after sleep deprivation is more effective than the simple or drug-induced sleep EEG. To investigate this, we recorded for 32 patients both sleep EEGs without sleep deprivation and, on the following day, sleep EEGs after 24 h of sleep deprivation. All the patients had atypical absences which were almost exclusively combined with generalized seizures or some other seizure types. All patients were receiving antiepileptic therapy. Sleep without sleep deprivation was induced by oral administration of 2 mg/kg body weight Protactyl (promazine hydrochloride). In patients showing no epileptic activity in the routine EEG, epileptic discharges could be provoked in 78% without sleep deprivation and in 72% after sleep deprivation. Epileptic activity was already seen in 28.1% of the cases in the awake EEG without sleep deprivation, recorded immediately before the sleep EEG, and in 50% of the cases in the awake EEG after sleep deprivation. It is unlikely that promazine hydrochloride in the dose used here has an additional inherent provocative effect. Generalized spike-and-wave complexes or sharp slow wave complexes which were combined twice with foci and runs of rapid spikes were recorded. In the sleep EEG without sleep deprivation, epileptic discharges were seen in the somewhat shallower stages (C leads to A leads to B leads to D) and, in the sleep EEG after sleep deprivation, in the somewhat deeper stages (D leads to C leads to B leads to A). Fewer epileptic discharges were elicited in patients who were older at the time of their first seizure. The illness was mild in patients whose sleep EEGs showed no epileptic activity. It is concluded that, as a rule, it is not necessary to record an EEG after sleep deprivation in patients with atypical absences whose routine EEGs show no epileptic activity; the drug-induced sleep EEG shows the same provocative effect.

Adolescent↗
PubMed2003

Interaction of alcohol and drugs in fatal poisonings.

In Finnish data from 1995-2000, 1006 fatal poisonings due to alcohol (ethanol), a single drug or both were statistically analysed in retrospect to evaluate the interaction between alcohol and drugs. In 53% of these cases, low concentrations of some common benzodiazepines were present. The median postmortem blood alcohol concentration (BAC) was 3.3 percent per thousand (w/w) in the 615 alcohol poisonings, but significantly lower, ranging from 1.3 to 1.7 percent per thousand, when promazine, doxepin, amitriptyline or propoxyphene were found together with alcohol. When levomepromazine, temazepam or zopiclone were present, the median BAC was also significantly lower, 2.5-2.7 percent per thousand. Citalopram and diltiazem did not exhibit a significant effect. The median BAC was significantly lower in cases with high concentrations than in those with low concentrations of a drug (excluding citalopram), suggesting a positive concentration-effect relationship. Fatal toxicity indices (FTIs) were calculated by relating the number of deaths caused by a drug to the corresponding sales figures. Promazine had an extremely high FTI, followed by levomepromazine, propoxyphene, doxepin and amitriptyline. The other drugs had relatively low FTIs. The results reflect not only the acute toxicity of a given drug-alcohol combination but also the manners of use and abuse of these drugs.

Adult↗
PubMed2005

Models of treatment with antipsychotics of the schizophrenic patients.

The aim of this study were to determine which antipsychotic are currently in use, to establish which doses are administrated to patients, to find out is there a practice of proscribing simultaneously more then one antipsychotic drug, to determine whether antipsychotic are proscribed in divided doses, to establish whether there is, besides antipsychotics, treatment with other medicaments (co-administration), especially with antiparkinsonics. The research (study) is epidemiological-clinical prospective, descriptive and analytical and it was conducted at University hospitals in Sarajevo, Tuzla and Mostar. Criteria for inclusion, non-inclusion and exclusion from the study were precisely defined as a mean for formation of sample. Based on this hypothesis were established, zero and alterative. According to zero hypothesis in the treatment of schizophrenia at University hospitals in FBiH new antipsychotic drugs are in use, small doses are proscribed (up to 20 mg), not more then one antipsychotic drug is used simultaneously, antipsychotics are administrated once a day and alongside with antipsychotics other medicaments are not co-administrated, especially antiparkinsons. The results of our study are showing that majority of patients are treated with classical antipsychotics. Minority of patients is treated with atypical neuroleptics like olanzapine, which is proscribed only in Sarajevo. Use of risperidone and ziprasidone is registered also only in Sarajevo, but only small number of patients is treated with these drugs. Most frequent antipsychotics were promazine and haloperidol. The range between minimal and maximal daily dose of promazine was from 50 to 450 mg/daily, and for haloperidol from 1 to 75 mg/daily. Above-mentioned drugs were administrated in an average from two to three times a day. Alongside with antipsychotics, other drugs were used. Most frequent was the use of biperidine in oral and parenteral formulation, as well as nitrazepam and diazepam. The importance of this study is following: data are useful for the current mental health care reform in FBiH, results will point out place and position of FBiH in contemporary world trends in the treatment of schizophrenia, they will contribute to rational use of antipsychotic therapy, they will point out possible ways in reduction of side effects, often dangerous adverse effects of antipsychotics, and they will give contribution to faster rehabilitation of schizophrenics with the reduction of financial means for the treatment of patients with schizophrenia.

Adult↗
PubMedDate not supplied

Pharmacokinetics of phenothiazine neuroleptics after chronic coadministration of carbamazepine.

The aim of the present study was to assess the influence of carbamazepine on the pharmacokinetics of the two phenothiazine neuroleptics thioridazine and perazine in rats. The obtained results are compared with the results of analogical experiments concerning promazine. Thioridazine or perazine (10 mg/kg i.p.) were administered twice a day for two weeks alone or jointly with carbamazepine (15 mg/kg i.p. during the 1st week, and 20 mg/kg i.p. during the 2nd week of treatment). Concentrations of the neuroleptics and their main metabolites in the plasma and brain were measured at 30 min, 6 and 12 h after the last dose of the drugs. Carbamazepine decreased the concentrations of thioridazine and its metabolites (especially mesoridazine and sulforidazine) in plasma at 30 min and 6 h after the last dose of the drugs. Similar changes in the concentrations of thioridazine and its metabolites were observed at 6 h in the brain. Carbamazepine did not significantly influence the pharmacokinetics of perazine. In vitro studies with liver microsomes of control rats revealed that carbamazepine added to the incubation mixture inhibited N-demethylation of thioridazine via mixed mechanism, but it did not influence significantly 2- or 5-sulfoxidation of the neuroleptic. In the case of perazine, no distinct inhibition of its N-demethylation or sulfoxidation by carbamazepine was observed. Neither carbamazepine nor the neuroleptics, administered separately or jointly for two weeks, significantly influenced the concentrations of cytochromes P-450 and b-5 in the liver. Carbamazepine++ given chronically decreased the rate of N-demethylation and had a tendency to accelerate 2-sulfoxidation of thioridazine, both when given alone (as compared to the control) and when coadministered with thioridazine (as compared to the thioridazine-treated group). In contrast, chronic treatment with carbamazepine alone, significantly increased the rate of perazine N-demethylation. When carbamazepine was coadministered with perazine, the effect was less pronounced. In conclusion, carbamazepine given jointly with thioridazine or promazine at pharmacological doses to rats accelerates the metabolism of the neuroleptics, which is not the case with perazine. The observed induction proceeds by metabolic pathways other than N-demethylation or sulfoxidation. The different effect of carbamazepine on the N-demethylation of thioridazine and perazine in liver microsomes of control and carbamazepine-treated rats implicates that the two reactions are not catalyzed by the same enzyme. Such an induction of neuroleptic metabolism by carbamazepine in patients may worsen psychotic symptoms.

Animals↗
PubMedDate not supplied

[Potentiation of the action of reserpine on the frog as a characteristic effect of antidepressants].

Antidepressants-thymoanaleptics chlorimipramine, amitriptyline, imipramine, melitracen potenciated the inhibitory effect of reserpine in a frog (supression of the turning over from the back reflex) stronger than did antidepressants with less marked thymoanaleptic action (Lu-5-003, azaphen, quipazine, desipramine) and also neuroleptics (promazine, stelazine, haloperidol) cholinolytics (atropine and benectyzine) and stimulator--phenamine. The potentiating action of tertiary amines--imipramine, amitriptyline protixen was stronger than that of the corresponding secondary amines (desipramine, norprotixen, nortriptyline). Phenothiazines with the chlorine atom in the second position (chlorprotixen and chlorpromazine) potentiated the effect of reserpine less intensively than did their chlorine-free analogues (protixen, promazine).

Amphetamine↗
PubMed1975

A benzodioxanhydroxyethylpiperidine derivative with an acute central hypotensive action, different from that of clonidine. A comparison with neuroleptic agents.

Ertyhro-1-(1-[2-(1,4-benzodioxan-2-yl)-2-OH-Et]-4-piperidyl)-2-benzimidazolinone (R28935), a new benzodioxanhydroxyethylpiperidyl derivative that is chemically but not pharmacologically related to pimozide, proved to possess potent central hypotensive activity when injected into the left vertebral artery of anaesthetized cats. Although almost as potent as clonidine, its hypotensive action is more prolonged. The central hypotensive effect is dose-dependent and stereospecific, the threo-isomer being much less effective than the erythro-form. In contrast to the effect of clonidine, the centrally induced hypotensive action of R 28935 is not diminished after pretreatment with piperoxane, yohimbine or desipramine. Accordingly, central alpha-adrenergic receptors are probably not involved in the central hypotensive action of R 28935. The following surgical interventions did not diminish the central hypotensive action of R 28935: bilateral vagotomy, bilateral cervical sympathectomy, bilateral extirpation of the stellate ganglia. Neuroleptic agents like pimozide, haloperidol, chlorpromazine and promazine were far less potent hypotensive agents. Promazine showed some central hypotensive action but the blood pressure-lowering effects of the other neuroleptic drugs are of peripheral origin and probably reflect the alpha-sympatholytic properties. From the results it si concluded that R 28935 depresses peripheral sympathetic tone via a centrally induced primary effect. Central alpha-adrenergic receptors do not play a role in this primary effect of R 28935, whereas they do play their part in that of clonidine or alpha-methyl-DOPA. As such, R 28935 is an example of a new class of centrally acting hypotensive compounds. Moreover, this compound provesthat it has been possible to separate the neuroleptic and hypotensive properties in benzimidazolinone derivatives.

Animals↗
PubMedDate not supplied

Myeloperoxidase-generated phenothiazine cation radicals inactivate Trypanosoma cruzi dihydrolipoamide dehydrogenase.

Peroxidase/H2O2/phenothiazine systems irreversibly inhibit Trypanosoma cruzi dihydrolipoamide dehydrogenase (LADH). Inactivation of the parasite enzyme depended on (a) phenothiazine structure; (b) peroxidase nature; (c) incubation time and (d) the presence of a cation radical scavenger. With the myeloperoxidase/H2O2/system, promazine, trimeprazine, thioridazine, promethiazine, prochlorperazine, chlorpromazine and perphenazine were the most effective derivatives out of twelve phenothiazines studied. An electronegative substituent at position 2 of the phenothiazine ring such as Cl, or trifluoromethyl, propionyl and nitrile groups decreased or nullified phenothiazine activity. Myeloperoxidase/H2O2/, horseradish peroxidase/H2O2/, and myoglobin/H2O2/systems activated phenothiazines producing the corresponding cation radicals, myeloperoxidase being the most selective one with respect to phenothiazine structure. The myoglobin/H2O2/system activated phenothiazines that were scarcely active or inactivate with the MPO/H2O2/system, such as the trifluoromethyl derivatives. Production of phenothiazine cation radicals was demonstrated by optical spectroscopy. Phenothiazine cation radical stability depended on their structure as illustrated by promazine and thioridazine. Thiol compounds (GSH, N-acetyl-cysteine and penicillamine), aromatic aminoacids (L-tyrosine, L-tryptophan, and the corresponding peptides) and ascorbate scavenged phenothiazine cation radicals, thus preventing LADH inactivation. Comparison of the summarized phenothiazine effects with those of phenothiazines on T. cruzi suggest the role of cation radicals in phenothiazines chemotherapeutic actions.

Amino Acids, Aromatic↗
PubMedDate not supplied

Gravimetric and spectrophotometric determination of some phenothiazine and imidazole derivatives in coated tablets and tablets.

Two drugs in the form of coated tablets: Promazin (promazine hydrochloride) (1) and Thioridazin (thioridazine hydrochloride) (2), and tablets Clotrimazolum (clotrimazole) (3) were assayed gravimetrically and spectrophotometrically in the same process using complexes with ammonium molybdate. Stoichiometry of these complexes was established by elemental analysis and analysis of the incineration residue (MoO3). The complexes were subsequently characterized using their IR and UV spectra and melting points. The active substances of the complexes were also determined spectrophotometrically. Using this method Beers Law was found to hold for the concentration ranges of 5-40 microg/ml (complex of 1), 5-60 (microg/ml (complex of 2) and 2-10 microg/ml (complex of 3). The method was validated in terms of precision, linearity, detection limit and quantification limit. The two methods of drug determination, used in a single analytical process verify each other.

Anti-Bacterial Agents↗
PubMedDate not supplied

Interactions between neuroleptics and CYP2C6 in rat liver--in vitro and ex vivo study.

The aim of the present study was to investigate the influence of classic and atypical neuroleptics on the activity of rat CYP2C6 measured as a rate of warfarin 7-hydroxylation. The reaction was studied in control liver microsomes in the presence of neuroleptics, as well as in microsomes of rats treated intraperitoneally for one day or two weeks (twice a day) with pharmacological doses (mg/kg) of the drugs (promazine, levomepromazine, thioridazine, perazine 10, chlorpromazine, haloperidol 0.3, risperidone 0.1, sertindole 0.05), in the absence of the neuroleptics in vitro. Some of the neuroleptics added in vitro to control liver microsomes decreased the activity of CYP2C6. Sertindole and levomepromazine (Ki = 25 and 31 microM, respectively) were the most potent inhibitors of the rat CYP2C6 among the drugs studied. Their effects were more pronounced than those of the other phenothiazines tested: thioridazine and chlorpromazine (Ki = 88 and 91 microM, respectively), promazine and perazine (Ki = 322 and 341 microM, respectively), risperidone (Ki = 414 microM) or haloperidol (Ki = 606 microM). The investigated neuroleptics--when given to rats in vivo for one day or two weeks--did not produce any indirect effect on CYP2C6 via other mechanisms, except for levomepromazine, which increased the activity of the enzyme after 24-h exposure. Therefore, the direct inhibitory effect of levomepromazine on CYP2C6 may be attenuated by an indirect mechanism at the beginning of the neuroleptic therapy. In summary, the obtained results show direct inhibitory effects of some phenothiazine neuroleptics and sertindole on the activity of CYP2C6 in vitro in rat liver microsomes. Considering relatively high pharmacological doses and therapeutic concentrations of phenothiazines, it seems that the inhibitory effect of levomepromazine (and other phenothiazines with Ki values below 100 microM) found in vitro may be of physiological and pharmacological importance in vivo.

Animals↗
PubMed2006

Inhibitory effect of antipsychotic drugs on the Con A- and LPS-induced proliferative activity of mouse splenocytes: a possible mechanism of action.

Antipsychotic drugs are widely used to alleviate a number of psychic disorders and have been found to modulate some immune parameters, but the molecular mechanism of their action on the proliferative activity has been poorly recognized. In the present study, we investigated effects of various antipsychotics on the proliferative activity of lymphocytes stimulated by concanavalin A (Con A) and lipopolysaccharide (LPS). Chlorpromazine (3 x 10(-6)-10(-4) M) showed the most potent effect in inhibiting 3H-thymidine incorporation into C57BL/6 mouse spleen cells stimulated by Con A and LPS. Treatment of the cells with thioridazine (10(-5)-10(-4) M), promazine (10(-5)-10(-4) M), haloperidol (10(-5)-10(-4) M), risperidone (10(-5)-10(-4) M), raclopride (3 x 10(-5) - 10(-4) M), remoxipride (3 x 10(-5)-10(-4) M) and clozapine ( 3 x 10(-5)-10(-4) M), but not with sulpiride (10(-7)-10(-4) M), suppressed proliferative activity of splenocytes after Con A stimulation. On the other hand, LPS-induced proliferation of splenocytes was inhibited by clozapine, promazine, thioridazine and haloperidol, but not by risperidone, remoxipride, sulpiride and raclopride. In the next part of the study, the influence of some kinase modulators on chlorpromazine- and clozapine-evoked inhibition of the proliferative activity of splenocytes was determined. Wortmannin, a selective phosphatidylinositol 3-kinase (PI3-K) inhibitor, blocked chlorpromazine and clozapine inhibitory effect on the mitogen-stimulated splenocyte proliferation. The involvement of PI 3-K /protein kinase B (PKB, Akt) pathway was confirmed by the results of the Western blot study, which showed that both drugs increased the level of active phospho-Ser-473 Akt, without changing the total Akt level, and decreased the level of active, nonphosphorylated glycogen synthase kinase-3 (GSK-3beta). Additionally, we have found that chlorpromazine action was also attenuated by a selective p-38-MAPK inhibitor, while clozapine effect was suppressed by a protein kinase C (PKC) activator. The obtained results indicated that atypical antipsychotic drugs markedly inhibited the proliferative activity of splenocytes only after ConA stimulation. Inhibition of the proliferative capability of splenocytes by chlorpromazine and clozapine resulted mainly from the activation of PI3-K/Akt pathway.

Androstadienes↗
PubMed1975

Rate-dependent Effects of drugs. II. effects of some major tranquilizers on multiple fixed-ratio, fixed-interval schedule performance.

The effects of promazine, chlorpromazine, triflupromazine, prochlorperazine, trifluoperazine, perphenazine, fluphenazine, haloperidol, benzquinamide, tetrabenazine and chlorprothixene were determined on the rate of conditioned key pecking of pigeons under a multiple fixed-ratio 30, fixed-interval 5-minute schedule of food presentation. Chlorpromazine, prochlorperazine, perphenazine, chlorprothixene and tetrabenazine decreased responding relatively more within the fixed-interval component than within the fixed-ratio component and also produced rate-dependent effects within the fixed interval component, increasing the low rates of responding early in the fixed-interval but decreasing the high rates of responding in the terminal parts of the fixed interval. Triflupromazine, trifluoperazine, fluphenazine and haloperidol also decreased responding relatively more within the fixed-interval component than within the fixed-ratio component, but did not produce rate-dependent effects within the fixed-interval component. Both low and high rates of responding within the fixed interval were decreased only by these four drugs and they produced small and inconsistent decreases in the quarter-life values. Promazine and benzquinamide decreased responding relatively more within the fixed-ratio component than within the fixed-interval component and also produced rate-dependent effects within the fixed-interval component. There was a structure-activity relationship between the chemical group on the benzene ring of the phenothiazine nucleus and the rate-dependent effect on responding within the fixed-interval component. Phenothiazines with a hydrogen or chlorine group on the benzene ring produced a rate-dependent effect on responding within the fixed interval, while phenothiazines with a trifluoromethyl group on the benzene ring did not produce a rate-dependent effect on responding within the fixed interval.

Animals↗
PubMed1964

SOME ACTIONS OF CENTRALLY ACTIVE AND OTHER DRUGS ON THE TRANSMISSION OF SINGLE NERVE IMPULSES THROUGH THE ISOLATED SUPERIOR CERVICAL GANGLION PREPARATION OF THE RABBIT.

The effect of some centrally-active and other drugs on the transmission of single nerve impulses through the isolated superior cervical ganglion preparation of the rabbit has been studied by recording both preganglionic and postganglionic action potentials. Block of conduction in the axon could be distinguished from block of the synaptic mechanism. The drugs did not appear to exert any one characteristic form of blocking action. A continuous spectrum of drug action linked an agent such as meprobamate which acted predominantly on the synapse to benactyzine which acted mainly by blocking axonal conduction. The drugs have been divided into three groups. Group I: hexamethonium, meprobamate, paraldehyde, amylobarbitone, methylpentynol and azacyclonal; these acted relatively selectively at the ganglion. Group II: N714C (the cis-isomer of chlorprothixene), prochlorperazine, methylpentynol carbamate, pipradrol, promethazine, perphenazine and procaine; the action of these drugs on the ganglion could be accounted for entirely in terms of their axonal depressant action. Group III: chlorprothixene, promazine, N720 (dihydrochlorprothixene), chlorpromazine, hydroxyzine and benactyzine; these drugs also blocked axonal conduction but in addition they appeared to exert a "facilitating" action at the ganglionic synapse. The actions of adrenaline, adrenochrome, iproniazid, ergotoxine, mescaline and lysergic acid diethylamide on transmission were also studied. The implications of the modifications of ganglionic transmission produced by these drugs is discussed.

Action Potentials↗
PubMed1964

A COMPARISON OF IMIPRAMINE, CHLORPROMAZINE AND RELATED DRUGS IN VARIOUS TESTS INVOLVING AUTONOMIC FUNCTIONS AND ANTAGONISM OF RESERPINE.

Seven structurally-related compounds consisting of three antidepressant drugs (imipramine, desmethylimipramine and amitriptyline), three tranquillizing agents (promazine, chlorpromazine and chlorprothixene) and a hybrid, desmethylpromazine, have been examined in a series of tests involving autonomic functions and antagonism of reserpine. Activities of the compounds in antagonizing reserpine-induced ptosis in rabbits and prolongation of alcohol hypnosis in mice give good correlation with their clinical actions, whilst their activities in augmenting excitation of rats by amphetamine and yohimbine toxicity in mice, and in reversing reserpine-induced bradycardia in rats offer further evidence for drug-induced sensitization to adrenergic or tryptaminic mechanisms, which is not however specific for antidepressant agents. No evidence has been obtained to indicate that a central parasympatholytic action is an important component of the antidepressant activity of imipramine and related drugs.

Alcoholic Intoxication↗
PubMed1963

THE METABOLISM OF THE VOLATILE AMINES. IV. THE ROLE OF DRUGS IN THE PATHOGENESIS OF HEPATIC ENCEPHALOPATHY.

The effects of certain drugs on metabolism of ammonia by the liver and kidneys in dogs were investigated by a technique in which both hepatic inflow and outflow bloods could be repeatedly sampled in unanesthetized healthy animals. Specific representatives of the classes of the drugs studied included thiopental (barbiturates), morphine (opiates and analgesics), promazine (tranquillizers), and chlorothiazide (oral diuretics).The three drugs commonly used as sedatives were all found to impair the ability of the liver to metabolize ammonia. The diuretic, by contrast, increased the amount of ammonia put into the systemic system by the kidneys. Ethanol appeared to have little or no direct effect on ammonia metabolism.The possibility exists that the occurrence of acute hepatic encephalopathy in patients with severe liver disease may be avoided in many cases if these drugs are administered with proper care. Results also indicated that current concepts of the pharmacological action of sedatives, opiates and tranquillizers may require revision.

Amines↗
PubMed1997

Neuroleptic prescribing to the community elderly in Nottingham.

DESIGN: A cross-sectional pilot survey of computerized prescribing databases and written general practitioner records. Data were abstracted by the first author using a standard proforma. SETTING: Six out of 12 general practices situated in an area of north Nottingham known to have a high density of residential and nursing homes cooperated with the exercise (one was excluded because it lacked a computer system, one because the principal had a specialist commitment to old age psychiatry and four were self-excluded). PATIENTS: Patients recorded as receiving repeat prescriptions of oral preparations of thioridazine, chlorpromazine, promazine, haloperidol or trifluoperazine. MEASURES: Point prevalence rates of neuroleptic repeat prescribing classed by age group and, in the case of the elderly, residential status. For elderly recipients: median (range) duration on neuroleptics, median (range) time since last review and numbers (percentages) having various characteristics. RESULTS: Elderly patients were found to be more likely consumers of neuroleptic medication than their younger counterparts. If these results are extrapolated nationwide, then approximately half the patients receiving repeat prescriptions for the commonest oral neuroleptics emerge as elderly and of these about half are in nursing/residential care. Patients in nursing/residential homes suffering dementia formed the largest group of recipients, but have the least monitoring by psychiatric teams. CONCLUSION: The result highlight a need for a close partnership between primary care, community care facilities and old age psychiatric teams to ensure adequate monitoring and the implementation of psychological strategies to minimize their use.

Age Factors↗
PubMed1981

A comparative study of the diagnosis value of drug-induced sleep EEGs and sleep EEGs following sleep deprivation in patients with complex partial seizures.

The purpose of the study was to investigate whether the sleep EEG after sleep deprivation has a stronger provocative effect than the drug-induced sleep EEG. For this purpose a sleep EEG, induced by 2 mg/kg body weight of promazine hydrochloride, was recorded. On the following day a sleep EEG of the same patient was recorded after sleep deprivation of 24--26 h. If only patients whose wake EEGs were free from epileptic activity are considered, the rate of provocation was 58%. As epileptic activity could be recorded even in the sleep EEG without sleep deprivation in 45%, the advantage gained by recording a sleep EEG after sleep deprivation (52%) is only relatively small. The occurrence of epileptic activity was shown to be significantly more frequent amongst women and those who developed epilepsy at a younger age. For practical purposes it is recommended that for those patients whose wake EEGs are free from epileptic activity, a sleep EEG--possibly drug-induced--should be recorded. Only in instances where epileptic activity can not then be recorded should a wake EEG after sleep deprivation be carried out, and followed immediately, if necessary, by a sleep EEG.

Adolescent↗