PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “OPIPRAMOL”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources
PubMed1978

Aggregation of antidepressant drugs in aqueous solution.

Light scattering, conductivity and pH methods have been used to examine the aggregation in aqueous solution of a series of antidepressant drugs. The drugs investigated included the hydrochlorides of amitriptyline, butriptyline, protriptyline, nortriptyline, imipramine, desipramine, clomipramine, dothiepin, dibenzepin, opipramol, iprindole, doxepin, mianserin and maprotiline. No significant association of dibenzepin, mianserin or maprotiline hydrochlorides could be detected up to their respective solubility limits. A micellar pattern of association was established for all other compounds. Critical micelle concentrations and micellar properties are reported.

Antidepressive Agents↗
PubMed1981

Effect of pH on the micellar properties of amphiphilic drugs in aqueous solution.

The influence of pH on the micellar properties of several amphiphilic drugs under conditions of constant ionic strength has been investigated. No significant effect of pH on the critical micelle concentration or micellar size of chlorpromazine hydrochloride was noted over a pH range well below the pKa. The micellar properties of opipramol, thiopropazate, flupenthixol, clopenthixol, and trifluoperazine, which contain a piperazine moiety showed considerable pH dependence. The concentration dependence of the pKa in these micellar systems was taken into consideration in the selection of pH values representative of complete protonation of either one or both of the piperazine N atoms. A lower aggregation number and higher critical micelle concentration was observed at a low pH corresponding to complete protonation of both charge centres. Mepyramine maleate exhibited a non-micellar mode of association at pH 5.5 which could be described by a stepwise association model in which association constants, KN, increased sequentially with aggregation number. N, according to the relationship, KN = K(N - 1)/N where K = 31.3 dm3mol-1. No significant association could be detected at pH 2 when the pyridine ring N was fully protonated.

Chlorpromazine↗
PubMed1998

Pharmacological analysis of sterol delta8-delta7 isomerase proteins with [3H]ifenprodil.

Sterol Delta8-Delta7 isomerases (SIs) catalyze the shift of the double bond from C8-9 to C7-8 in the B-ring of sterols. Surprisingly, the isoenzymes in fungi (ERG2p) and vertebrates [emopamil binding protein (EBP)] are structurally completely unrelated, whereas the sigma1 receptor, a mammalian protein of unknown function, bears significant similarity with the yeast ERG2p. Here, we compare the drug binding properties of SIs and related proteins with [3H]ifenprodil as a common high affinity radioligand (Kd = 1.4-19 nM), demonstrating an intimate pharmacological relationship among ERG2p, sigma1 receptor, and EBP. This renders SIs a remarkable example for structurally diverse enzymes with similar pharmacological profiles and the propensity to bind drugs from different chemical groups with high affinity. We identified a variety of experimental drugs with nanomolar affinity for the human EBP (Ki = 0.5-14 nM) such as MDL28815, AY9944, triparanol, and U18666A. These compounds, as well as the fungicide tridemorph and the clinically used drugs tamoxifen, clomiphene, amiodarone, and opipramol, inhibit the in vitro activity of the recombinant human EBP (IC50 = 0.015-54 microM). The high affinity of the human EBP for 3H-tamoxifen (Kd = 3 +/- 2 nM) implies that the EBP carries the previously described microsomal antiestrogen binding site. Interactions of the EBP with structurally diverse lipophilic amines suggest that novel compounds of related structure should be counterscreened for inhibition of the enzyme to avoid interference with sterol Delta8-Delta7 isomerization.

Adrenergic alpha-Antagonists↗
PubMed2006

A retrospective analysis of antidepressant poisonings in the emergency department: 11-year experience.

Between 1993 and 2004, patients with antidepressant poisoning admitted to an emergency department (ED) were analysed retrospectively with regard to demographics, clinical findings and treatment attempts. Age, gender, suicide attempts, classification of antidepressants, Glasgow Coma Scale (GCS) score, ECG findings, need for endotracheal intubation, follow-up period and Antidepressant Overdose Risk Assessment (ADORA) criteria were analysed by SPSS software. A total of 356 antidepressant poisoning cases were evaluated. Tricyclic antidepressants (TCA), especially opipramol and amitriptyline, were the most common agents (58.4%). The most frequent ECG finding was sinus tachycardia (40.7%, n=145). Endotracheal intubation was required in 9.6% of cases. Patients with TCA ingestion had a longer observation time in the ED, abnormal ECG findings, abnormal physical examination findings and more ADORA criteria, than patients who ingested selective serotonin re-uptake inhibitors (SSRI) (P = 0.008, P = 0.008, P < 0.001, P < 0.001). It was found that the patients who ingested TCA (P = 0.001), poisoned with amitriptyline (P = 0.001), patients with GCS scores of 8 and less (P = 0.001), patients with two or more ADORA criteria (P = 0.001), with seizures (P = 0.001), with abnormal ECG (P = 0.012), and patients with a history of two or more suicide attempts were intubated more frequently. Suicide attempts, classification of the antidepressant, ECG findings, seizure, GCS score and number of detected ADORA criteria affect the need for intubation in patients with antidepressant poisoning.

Adolescent↗
PubMed2003

Therapeutic drug monitoring of 13 antidepressant and five neuroleptic drugs in serum with liquid chromatography-electrospray ionization mass spectrometry.

Therapeutic drug monitoring of antipsychotic drugs has become more and more important in recent years, and a well-organized therapeutic drug monitoring service with fast turn-around times is very important. Therefore, an analytical method coupling high-performance liquid chromatography to mass spectrometry with electrospray ionization in the positive mode was established in our laboratory. Amitriptyline, citalopram, clomipramine (including norclomipramine), desipramine, dibenzepin, doxepin (including nordoxepin), escitalopram, flupentixol, fluphenazine, fluvoxamine, imipramine, nortriptyline, opipramol, pipamperone, reboxetine, thioridazine, trimipramine and zuclopenthixol were separated on a reversed-phase C18 column. The mobile phase consisted of acetonitrile and ammonium acetate buffer pH 4. Because of different organic solvents used for the liquid-liquid extraction and the different volumes of mobile phases in which the residues were dissolved, four analytical systems had to be applied. Within the run-time of maximal 10 minutes the 13 antidepressant and five neuroleptic drugs were baseline separated on the corresponding mass-to-charge track. The calibration range of each drug was linear, all between-day coefficients of variation were below 7% and the recovery rates were between 60 and 103%. Using 1 ml of serum, the lower limits of quantification were between 1.2 and 54 nmol/l for the different drugs and below the therapeutic range for each of the different drugs.

Antidepressive Agents↗
PubMed1988

Differences in adipose tissue distribution of basic lipophilic drugs between intraperitoneal and other routes of administration.

1. Distribution of 14C-methadone in male rats was studied after administration of single i.p. doses. Highest concentrations were attained after 30 min in the decreasing order of abdominal adipose tissues, liver, lung, other organs. Concentrations in abdominal adipose tissues were 20 times higher than in subcutaneous adipose tissue. This is in contrast with what occurs with other routes of administrations, where only low concentrations are attained in both subcutaneous and abdominal adipose tissues. 2. The situation in the peritoneal cavity after i.p. injection was simulated in vitro by incubation of whole, excised abdominal adipose tissues of rats with methadone and other basic drugs (dibenzepine, alprenolol, opipramol, propranolol, chlorpheniramine, desipramine, imipramine and chlorpromazine) for 6 h at pH 7.4. These drugs were readily taken up (25 to 74% at equilibrium). 3. There was a positive correlation between uptake and lipophilicity of the drugs as measured by log P (octanol/water). Less lipophilic drugs such as amphetamine, morphine and chlorphentermine were not appreciably taken up from the incubation medium. The threshold log P-value for appreciable adipose tissue uptake is around 2. 4. It is concluded from these data and related studies that basic lipophilic drugs are not stored in adipose tissues in vivo, except when given via the i.p. route. In the latter case the storage appears to result from non-systemic, diffusional uptake from the peritoneal cavity.

Adipose Tissue↗
PubMed2002

The treatment of generalised anxiety disorder. A systematic review.

We have reviewed the treatment of generalised anxiety disorder (GAD). Previous systematic reviews, clinical guidelines, and controlled trials were critically appraised, and described. Cognitive therapy, anxiety management therapy, certain antidepressants (paroxetine, imipramine, trazodone, opipramol), benzodiazeines and buspirone are effective treatments for GAD. The application of these findings in the clinical situation was discussed.

Anxiety Disorders↗
PubMed1992

High-affinity dextromethorphan and (+)-3-(-3-hydroxyphenyl)-N-(1-propyl)piperidine binding sites in rat brain. Allosteric effects of ropizine.

Dextromethorphan (DM) binds to high- and low-affinity sites in the rat brain. The high-affinity DM binding is inhibited by nonnarcotic antitussives, opipramol and sigma ligands with nanomolar affinities. Computer-assisted modeling of homologous and heterologous competition studies between DM and (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine [(+)-3-PPP] were performed at pH 8.4. These experiments confirmed the existence of the common high-affinity DM1/sigma 1 site (R1) for which DM and (+)-3-PPP have Kd values of 20 and 10 nM, respectively. DM also binds to a second high-affinity site (R2, Kd, 20 nM) for which (+)-3-PPP has only micromolar affinity. Similarly, (+)-3-PPP binds to another high-affinity site (R3, Kd, 60 nM) for which DM has micromolar affinity. The common high-affinity DM1/sigma 1 site is allosterically modulated by the anticonvulsant ropizine, and is (+)-pentazocine sensitive, as is the homologous site in the guinea pig. However, in the rat the common DM1/sigma 1 site is 10 times smaller than in the guinea pig. This explains the apparently different effects of the allosteric modifiers in both species. The multiplicity of binding sites for DM and (+)-3-PPP resolved in this investigation will help to establish the physiological role and the pharmacological potential of the different sites. Meanwhile, the pharmacological effects of DM and sigma ligands cannot be summarily attributed to any particular binding site or receptor. This investigation also demonstrates that the use of multiple labeled and unlabeled ligands, combined with computer-assisted modeling, is essential to resolve multiple binding sites with similar affinities and to characterize the complex effects of allosteric modifiers.

Allosteric Regulation↗
PubMed2005

Anti-proliferative activity of haloperidol in B16 mouse and human SK-MEL-28 melanoma cell lines.

Sigma receptors are present in cancer cell lines. The aim of the present study is to evaluate the anti-tumor activity of a series of sigma 1, sigma 2 and sigma 1/2 ligands in B16 melanoma cell lines. Proliferation, apoptosis, intracellular ATP content, cell cycle and molecular regulators were analyzed. Cell growth was determined using the sulforhodamine B (SRB) colorimetric cytotoxicity assay. Apoptosis was assessed by flow cytometry and DNA fragmentation, using ELISA cell death assay. ATP content was measured spectrofluorometrically and cell cycle analysis was performed by flow cytometry. The cytoplasmic and nuclear expression of cell cycle regulatory molecules, cyclin D and CDK2 (cyclin dependent kinase 2) were determined by Western blot analysis and quantified by densitometry. The sigma ligands in single digit micromolar concentrations inhibited B16 and multidrug-resistant B16 COL/R cell growth, leading to cell death at higher concentrations. The potency order was: haloperidol, reduced-haloperidol, ifenprodil tartrate, opipramol and carbetapentane citrate. B16 COL/R cells were to some extent, less sensitive to sigma ligands. Further studies have shown that the growth inhibitory effect of sigma ligands could be attributed to G1 arrest of the cell cycle, mediated by a marked decrease in cytoplasmic and nuclear cyclin D and CDK2 protein expression, though haloperidol induced loss of cell viability due to apoptosis. Sigma ligands induced an early decrease in ATP content. These data stimulated us to examine the combined anti-proliferative activity of haloperidol and the tyrosine kinase inhibitor imatinib mesylate (STI 571), on SK-MEL-28 human melanoma cells. Preliminary experiments demonstrated a marked synergistic interaction between the two agents.

Adenosine Triphosphate↗
PubMed1989

High affinity dextromethorphan binding sites in guinea pig brain. Effect of sigma ligands and other agents.

Dextromethorphan (DM), a non-narcotic antitussive, binds in the guinea pig brain to specific high- and low-affinity sites with Kd values of 57 nM and 24 microM, respectively (Musacchio et al., 1988). The antitussives carbetapentane, caramiphen, butamirate and dimethoxanate competed with the high-affinity binding of [3H]DM at pH 7.4 with nanomolar Ki values. Sigma site ligands showed high affinity for [3H]DM binding sites. The rank order of potency was: haloperidol greater than (+)-pentazocine greater than (+)-cyclazocine greater than 3-(-3-hydroxyphenyl)-N-(1-propyl)piperidine greater than (+)-N-allylnormetazocine greater than (-)-butaclamol much greater than (+)-butaclamol (-)-N-allylnormetazocine. The antipsychotic perphenazine competed with low nanomolar Ki values, whereas rimcazole was weaker. The antidepressant opipramol and the benzomorphan (+)2'methoxyphenazocine were the most effective drugs tested, with Ki values of 0.4 nM. By contrast, MK-801 and phencyclidine hydrochloride were very weak competitors for [3H]DM binding. The diphenylalkylamines were the most effective competitors of the calcium channel blocking agents: prenylamine and cinnarizine had Ki values of 17 and 22 nM, respectively. Lidoflazine and hydroxyzine were slightly less potent, but nifedipine and the benzothiazepine diltiazem were much weaker. Potassium channel blockers inhibited DM binding in pharmacologically relevant concentrations: primaquine was the most effective with a Ki of 0.5 microM. Other antimalarial potassium channel blockers tested inhibited binding in the micromolar range. 4-Aminopyridine and tetraethylammonium had Ki values of 0.76 and 1.40 mM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Tricyclic antidepressants and dextromethorphan bind with higher affinity to the phencyclidine receptor in the absence of magnesium and L-glutamate.

Recent studies from our laboratory have provided evidence that multiple states of the phencyclidine (PCP) receptor exist. In addition, several compounds such as PCP and the novel anticonvulsant MK-801 were found to inhibit binding more potently in the presence of Mg2+ and L-glutamate (L-GLU) than when these agents were excluded from the binding assay. In the present study, a number of pharmacological compounds that have been suggested to interact within the N-methyl-D-aspartate (NMDA) receptor complex, including tricyclic antidepressants (TCAs), were examined for their ability to inhibit the binding of [3H]1-[1-(2-thienyl)cyclohexyl]piperidine [( 3H]TCP) in the absence or presence of Mg2+ and L-GLU. The TCAs imipramine, amitriptyline, and opipramol produced shallow inhibition curves in the absence of Mg2+ and L-GLU. Computer analysis of the binding data indicated that a two-component binding model described the data significantly better than a one-component model. In the presence of Mg2+ and L-GLU, the inhibition curves became steeper and were shifted to the right, and computer analysis of the binding data indicated that a one-component model adequately described the binding data. A series of other centrally active compounds, including several antipsychotics and antihistamines, the antiparkinsonian anticholinergic trihexyphenidyl and the antitussive dextromethorphan, were also found to be affected similarly by the inclusion of Mg2+ and L-GLU in the binding assay. Dextrorphan, in contrast to dextromethorphan, inhibited [3H]TCP binding more potently in the presence of Mg2+ and L-GLU. The present results suggest that the compounds that inhibit binding more potently in the absence of Mg2+ and L-GLU are interacting with the PCP receptor in a different manner from that of PCP and MK-801, because these open-channel blockers inhibit [3H]TCP binding more potently in the presence of Mg2+ and L-GLU. The data support previous findings that TCAs interact with the NMDA receptor complex and suggest that the compounds trihexyphenidyl and dextromethorphan, which have been shown to block NMDA-mediated neurotoxicity, may produce their effects through an interaction with the PCP receptor, albeit by a different mechanism from that of open-channel blockers.

Animals↗
PubMed1982

High performance liquid chromatographic determination of clocapramine in feed and plasma.

A high performance liquid chromatographic method is described for the determination of clocapramine in animal feed and plasma. Samples are made alkaline and then extracted with chloroform containing opipramol as internal standard. For plasma samples, the organic phase is evaporated to dryness under a stream of nitrogen, and the residue is dissolved in dichloromethane-methanol. Extracts are chromatographed on silica gel with dichloromethane-methanol-ammonia (100 + 10 + 0.25) as eluant, and quantitated using an internal standard. Within-day precision for plasma extracts (n = 15) was 3.39, 5.7, and 4.13% at 5, 10, and 15 mg clocapramine/L plasma, respectively, and day-to-day precision was 4.6, 6.8, and 4.4% at the same levels. The detection limit was 0,5 mg/L. Recovery from feed over the concentration range 2-6 g/kg was greater than 96%.

Animal Feed↗
PubMed1980

The effect of antidepressants on L-5HTP-induced changes in rat plasma corticosteroids.

The finding that L-5HTP will cause an elevation in rat plasma corticosteroids, presumably through generation of serotonin, has been utilized to evaluate the serotonin potentiating and antagonizing properties of a series of antidepressants. Fluoxetine and zimelidine were most effective in enhancing the effect of low dose (12. 5 mg/kg) L-5HTP. Agents such as chlorimipramine, viloxazine and opipramol were weakly active at potentiating L-5HTP and mianserin and dibenzepine were strong antagonists of the L-5HTP effect. Since antidepressants have been found to either potentiate or antagonize serotonin, it is difficult to envision that the antidepressants exert their therapeutic effect through serotongeric mechanisms.

5-Hydroxytryptophan↗
PubMed1994

Purification and amino-terminal sequencing of the high affinity phenylalkylamine Ca2+ antagonist binding protein from guinea pig liver endoplasmic reticulum.

A high affinity phenylalkylamine Ca2+ antagonist binding polypeptide (Moebius, F. F., Burrows, G. G., Striessnig, J., and Glossmann, H. (1993) Mol. Pharmacol. 43, 139-148) was purified to homogeneity from the endoplasmic reticulum of guinea pig liver with the aid of [3H]emopamil, an antiischemic agent, and [3H]azidopamil, a photoaffinity label. The purified protein retained its high affinity for the antiischemic drugs emopamil (Kd = 4 nM), opipramol (IC50 = 15 nM), trifluoperazine (IC50 = 2 nM), and for Zn2+ (IC50 = 2 microM). Ferguson plots revealed a molecular mass of 27.2 kDa. Partial amino acid sequence information was obtained by Edman degradation and revealed no homology to known protein sequences. Antibodies raised against a synthetic peptide corresponding to the first 25 NH2-terminal amino acid residues specifically immunoprecipitated the [3H]azidopamil photoaffinity-labeled polypeptide and recognized the protein in Western blots. Cross-linking with a variety of homo- and heterobifunctional agents lead to the formation of dimers. Since in the purified preparation no other subunit could be identified with different protein stains, our results indicate that the [3H]emopamil binding site is formed by the homodimer of a novel membrane protein.

Amino Acid Sequence↗
PubMedDate not supplied

Effect of thymoanaleptic agents on the course of experimental arterial hypertension and catecholamine content in tissues and urine.

Experimental hypertension was induced in rats by two methods. In the course of hypertension development the rats of experimental groups were treated with following tricyclic antidepressive agents: Imipramine, Opipramol, Amitriptylline and Nortriptylline injected in doses of 5.0 or 0.5 mg per 1 kg of body weight. Higher doses of the above drugs inhibited the development of hypertension, whereas the lower doses had no effect on arterial blood pressure.

Animals↗