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PubMed1975

Beta-phenylethylamine and locomotor activity in mice. Interaction with catecholaminergic neurones and receptors.

Beta-Phenylethylamine on injection into mice produced both an early and late phase of increased locomotor activity. The early phase produced by 50 mg phenylethylamine/kg was inhibited by pretreatment with phenoxybenzamine, phentolamine, alpha-methyl-tyrosine, diethyldithiocarbamate, pimozide and haloperidol, but not by propranolol, protriptyline and reserpine. The late phase produced by 100 mg phenylethylamine/kg was blocked only by pimozide and haloperidol, both of these in doses at least ten times higher than those required to block the early phase. From these results it was concluded that the increased early phase of locomotor activity was due to the release of dopamine and noradrenaline synthetic pathway, but not intact reserpine sensitive amine stores. In contrast the late phase of locomotor activity was independent of catecholamine stores and appeared to be produced by a direct action by either phenylethylamine or metabolites on dopamine receptors.

Animals↗
PubMed1990

Sleep apnoea syndrome--a study of 5 cases.

Sleep apnoea syndrome (SAS) is common in the West but its prevalence is uncertain in Southeast Asia. Five Chinese patients seen in a Sleep Assessment Unit in Hong Kong are presented to illustrate the spectrum of clinical features and treatment methods involved in obstructive and central sleep apnoea. The first patient is a 45-year old woman with severe obstructive SAS and cardiopulmonary complications who improved significantly after tracheostomy. The second patient is a 43-year old man who improved with weight reduction and protriptyline. The third is a 42-year old man whose SAS did not improve with uvulopalatopharyngoplasty but with continuous positive airway pressure (CPAP). The fourth is a 12-year old girl with obstructive SAS who improved significantly after tonsillectomy. The last patient is a 52-year old man with central SAS who improved with CPAP.

Child↗
PubMedDate not supplied

[Pharmacologic control of breathing].

Recent advances in respiratory neuropharmacology and neurophysiology have allowed the assessment of the effects of different drugs on the control of the ventilation both qualitatively (alterations of ventilatory pattern) and quantitatively (size and duration of the ventilatory and haemogasometric alterations). In the control mechanism of ventilation, the pharmacological intervention can act both on the respiratory input (basal metabolism, peripheral chemo-receptors, pulmonary receptors, bulbar neurons, cortical nervous system) and on the respiratory output (respiratory muscles). Based on personal experience in this field and the recent literature, the Authors briefly discuss the seat and the mechanism of action of the drugs with stimulating effect (respiratory analeptics, almitrines, progesterone, acetazolamide, salicylates, protriptyline, theophylline) and depressing effect (narcotics and narcotic-antagonists, anaesthetics, barbiturates and benzodiazepines) on the ventilation, as well as the role of the neurotransmitters and modulators. The clinical (positive and negative) effects of these drugs, particularly related to the patients with chronic lung disease, are also illustrated.

Central Nervous System Stimulants↗
PubMed1989

Treatment of affective illness in the elderly with drugs and electroconvulsive therapy.

Affective illness is common, frequently debilitating, and sometimes life-threatening in the elderly. Considerations pertaining to treatment with heterocyclic drugs, MAOIs, lithium, psychostimulants and thyroid hormone, as well as ECT, have been reviewed. Amitriptyline and imipramine cause significant orthostatic hypotension and probably should be avoided in the elderly. In addition, amitriptyline is extremely anticholinergic. Amoxapine is essentially a neuroleptic sequelae, including tardive dyskinesia. If a patient has had a prior positive response or has a relative who had a good outcome from a particular drug, it may be best to begin treatment with that drug. Initial choice of antidepressant can be based largely on the clinical picture. For example, if a depressed patient is sleeping much more than usual, try a potentially activating agent like desipramine or protriptyline. if, on the other hand, the patient is unable to sleep, a more sedating agent like nortriptyline, maprotiline, trimipramine, or trazodone should be tried. Risks and side effects of these drugs, as well as their use in cardiac patients, have been reviewed in detail. Many clinicians avoid MAOIs in elderly patients because of fear of adverse reactions. This fear is largely unfounded. Precautions, side effects, and specific recommendations have been outlined. Using lithium in the elderly requires special precautions because of decreased GFR and potential interactions with concomitantly used drugs. This paper has discussed possible side effects and toxicity. The usage of psychostimulants, such as methylphenidate and amphetamine, to treat medically ill depressed patients is reviewed. These agents are also sometimes useful in demented individuals or in patients with abulic frontal lobe syndromes. Poststroke depressions are common, and recent evidence indicates that they can be adequately treated. Stroke patients have many difficulties dealing with rehabilitation and should not be forced to suffer concomitant depression when we have the tools at hand to effectively treat such symptoms. Recent data on the potentiation of antidepressant effects by lithium or T3 indicate that they may be useful adjuvants in some tricyclic-resistant patients. Risks, side effects, and recent procedural advances in the use of ECT have been reviewed. Electroconvulsive therapy is both more effective and faster-acting than drugs in the treatment of depression. Many depressed elderly patients, especially those with psychotic symptoms, do not respond to drugs but improve with ECT.

Aged↗
PubMed1988

Reliability of antidepressant assays: a reference laboratory perspective on antidepressant monitoring.

Chromatography (gas and liquid) and immunoassays are used for monitoring the commonly prescribed tricyclic antidepressants. Many commercially available immunoassays are known to cross react with structurally similar compounds. Chromatographic methods make it possible simultaneously to resolve and quantify amitriptyline, nortriptyline, imipramine, desipramine, trimipramine, doxepin, desmethyldoxepin, protriptyline, and maprotiline-and potentially crossreactive compounds can be separated from the tricyclics. Immunoassays may have a valuable role in initial toxicological screening for the presence of a tricyclic-like compound, and they also may be helpful in a laboratory dedicated to a well-controlled patient group. However, 10% of our specimens contain more or different antidepressants than we are requested to analyze for. With our analysis, we are able to report which antidepressants are present, and in what concentrations. Further, in the case of a potential overdose of tricyclic, the primary purpose for early toxicological analysis to anticipate subsequent clinical complications. Therefore, even in the case of toxicological analysis, it is important to know exactly what tricyclic antidepressant is present rather than just the semiquantitative presence of one or more structurally related compounds, because these various compounds differ markedly in their potential for adverse effects. There are too many potential, and possibly yet unknown, interactions for a reference laboratory routinely to rely on immunoassays for therapeutic drug monitoring or toxicological identification of antidepressants.

Antidepressive Agents, Tricyclic↗
PubMed1979

Elimination of F'lac plasmid by different psychotropic drugs and some related compounds.

Desipramine, trimipramine, protriptyline, noxiptyline, promazine, trimeprazine, triflupromazine and chlorprothixene methoiodide eliminated the F'lac plasmid of Escherichia coli, while thiazinanum, toluidine blue, lidocaine and procaine were ineffective in this respect. The plasmid eliminating action of the drug ceased in the presence of 0.05 M magnesium sulphate. Methylene blue did not inhibit plasmid elimination by the psychotropic drugs, and in presence of the dye even lidocaine and procaine became effective. Based on plasmid elimination in the presence of methylene blue and on the selective effects of the lon- mutant, the plasmid eliminating mechanism of psychotropic drugs seems to differ from that of acridine orange.

Animals↗
PubMedDate not supplied

Liquid chromatographic determination of organic nitrogenous bases in dosage forms: a progress report.

A liquid chromatographic (LC) method has been developed as a general procedure for the assay of the salts of organic nitrogenous bases in a variety of dosage forms. The method uses a nitrile-bonded reverse phase column, a methanol-0.003M ammonium acetate (90 + 10) mobile phase, and photometric detection at 254 nm. The sample is dissolved in the mobile phase and an aliquot is injected through a 20 microL injection loop. Average recovery values for duplicate assays were chlorpheniramine maleate injection 97.8%, chlorpheniramine maleate tablets 99.1%, cyclizine hydrochloride tablets 100.0%, doxylamine succinate tablets 103.3%, mesoridazine besylate tablets 100.4%, pentazocine hydrochloride tablets 103.0%, promethazine hydrochloride injection 98.4%, protriptyline hydrochloride tablets 101.2%, pyrilamine maleate tablets 97.8%, pyrimethamine tablets 100.0%, tripelennamine citrate elixir 100.0%, and tripelennamine hydrochloride tablets 97.2%. Results by this method were in good agreement with those obtained by the USP XX method. This study, which is being continued, will be expanded to include additional drugs.

Chromatography, Liquid↗
PubMed1978

[Quantitative determination of tricyclic antidepressant drugs by high-pressure liquid chromatography (author's transl)].

With regard to the increasing importance of determining plasma levels of antidepressant drugs a procedure has been worked out which makes it possible to analyze these substances in a simple and sensitive way. 5 ng )ca. 20 pmol) amitriptyline, nortriptyline, imipramine, desmethylimipramine, chlorimipramine, desmethylchlorimipramine, and protriptyline can be detected with a high-pressure liquid chromatograph and a UV-monitor without prior derivatisation. The extraction is made from 1 ml serum. Because of their retention time the substances can be identified. This fact allows simultaneous analyzation of all tricyclic antidepressants.

Antidepressive Agents, Tricyclic↗
PubMed1980

Electrocardiographic changes in rats during chronic treatment with antidepressant and neuroleptic drugs.

Five antidepressants, 3 phenothiazines and 5 butyrophenone neuroleptics were administered to rats orally at maximally tolerated doses for 22 weeks. The electrocardiogram (ECG) was recorded weekly. In animals treated with antidepressants quinidine-like changes of the atrioventricular and intraventricular conduction developed. There were also elevation of T-wave and right rotation of the electrical axis. Dibenzepine had the least effect on the ECG. In the group of phenothiazines chlorpromazine induced tachycardia and thioridazine widening of the QRS complex. Prothipendyl had no effect. ECG-changes induced by some of the butyrophenone derivatives were tachycardia and widening of the QRS-complex. In rats treated with protriptyline the ECG changes were correlated with drug concentrations in serum and myocardial tissue. The studies provided a quantitative assessment of the cardiac effects of clinically proven psychotropic drugs. They will be useful as a baseline for the preclinical evaluation of new derivatives.

Animals↗
PubMed1978

Liquid-chromatographic procedure for tricyclic drugs and their metabolites in plasma.

We describe a procedure for determining amitriptyline and imipramine and their active metabolites nortriptyline and desipramine, respectively, at therapeutic concentrations in human plasma by use of liquid chromatography. The drugs are extracted at pH 10.5 into hexane/isoamyl alcohol, which is evaporated and the residue chromatographed. Protriptyline is used as the internal standard. As little as 10 microgram of each drug per liter could be detected in plasma, the limit being established by variability in drug-free plasmas. The day-to-day coefficient of variation for each drug at a concentration of about 100 microgram/liter was about 7%. Doxepin and diphenhydramine interfere with the analysis of amitriptyline. Total analysis time for a single sample is 20 min.

Amitriptyline↗
PubMed1984

[Sleep apnea syndrome].

The occurrence of episodes of obstructive apnoea during sleep is encouraged by a variety of factors: local anatomical abnormalities, degree of activation of the autonomous nervous system, obesity, central nervous system depression from alcohol or drug consumption, deprivation or fragmentation of sleep. Each of these factors can play a predominant role in the development of the syndrome and their demonstration can contribute to our understanding of the success or failure of the different treatments. The authors' therapeutic experience includes mainly healthy living associated with treatment of systemic disorders and use of medroxyprogesterone and protriptyline. These therapeutic measures can be supplemented, if needed, by palatopharyngoplasty with or without temporary tracheostomy.

Autonomic Nervous System↗
PubMedDate not supplied

The influence of psychotropic drugs on the phosphodiesterase activity in the rat brain meninges.

Phosphodiesterase (PDE) is present in brain meninges. Its activity is higher in the pia than in the dura mater. Phenothiazine neuroleptics: fluphenazine, trifluoroperazine, thioproperazine, chloropromazine and thioridazine at concentration 10(-5)--10(-4) M in vitro inhibit the PDE activity in the pia and dura mater. Most potent in this respect were fluphenazine and trifluoroperazine. Much less pronounced inhibition of PDE activity in brain meninges was found after in vitro administration of tricyclic antidepressant: nortriptyline, chlorimipramine, protriptyline, desipramine and imipramine in concentrations 10(-4)--10(-3) M. Administered in vivo in a dose of 0.1 mg or 5 mg/kg ip fluphenazine inhibited the hydrolysis of 32P-cAMP injected into subarachnoid space. The results indicate that PDE present in the rat brain meninges may control the cAMP level in the cerebrospinal fluid. Treatment with phenothiazine neuroleptics which inhibit the PDE activity in meninges may significantly depress the hydrolysis of cAMP in the cerebrospinal fluid.

Animals↗
PubMed1984

CNS effects of citalopram, a new serotonin inhibitor antidepressant (a quantitative pharmaco-electroencephalography study).

Citalopram, a new phthalane derivative and a specific serotonin re-uptake inhibitor in animal pharmacological tests, was evaluated in a double-blind, crossover, quantitative pharmaco-EEG (QPEEGTM) study in healthy human volunteers. The CNS effects of citalopram are linear, dose- and time-related, can statistically be differentiated from placebo, and indicate a rapid onset of effects with short duration. According to the Computer Data Bank, citalopram has a mode of action similar to mood elevators (antidepressants) with fewer sedative properties. Thus the therapeutic action of citalopram is predicted to be similar to desipramine and protriptyline from the tricyclics, and fluvoxamine from non-tricyclics. According to data bank assessment, it is hypothesized that the single antidepressant dose of citalopram is to be more than 25 mg, which should be given t.i.d. in clinical trials.

Adult↗
PubMed1984

Liquid-chromatographic determination of eight tri- and tetracyclic antidepressants and their major active metabolites.

A "high-performance" liquid-chromatographic method is presented for monitoring the therapeutic concentrations, in plasma, of eight tri- and tetracyclic antidepressants (amitriptyline, nortriptyline, imipramine, desipramine, doxepin, clomipramine, maprotiline, and protriptyline) and their major active metabolites. One of two internal standards is added to 0.5 mL of drug-containing plasma, the pH is adjusted to about 9.5 with borate buffer, and the sample is extracted with isoamyl alcohol in hexane. The extracts are chromatographed on a column of silica and absorbance of the effluent is measured at either 214 or 254 nm. Chromatographic response is linearly related to concentration for all components over a 5-500 ng range. Analytical recovery of the drugs and metabolites from plasma is approximately 75 to 85% at low and high concentrations. Within-run and day-to-day precision (CV) is less than 5% for both high and low concentrations of most of these drugs and metabolites. Parallel analysis of clinical samples by gas chromatography indicates that results by the two techniques are comparable. We report some results of therapeutic monitoring of clinical samples.

Antidepressive Agents↗
PubMed1984

Pineal aryl acylamidase: effects of melatonin, serotonin-related compounds, beta-carbolines, RO4-4602 and antidepressants.

The pineal aryl acylamidase (AAA) activity has been demonstrated and characterized for the first time using ONAc as a substrate. The pineal AAA activity in the presence of 0.05% Triton X-100 was linear with protein concentration up to 1 mg and with incubation time up to 1 hour. Both the rat and bovine pineal showed a pH optimum at 5.0. The in vitro and in vivo effects of several classes of drugs on the pineal AAA activity were examined. At 0.1 mM, 5-HT, N-acetyl-5HT, melatonin, d-LSD, l-LSD, methiothepin, DA, chlorimipramine, imipramine, pargyline, TH C and harmaline significantly inhibited the rat pineal AAA activity by 19-51%. N-Acetyl-5-HT was the most potent in vitro inhibitor. However, at the same concentration, NE, 6-MeO-harman and eserine did not show any effect on the enzyme activity. Lineweaver-Burk plot indicated a competitive type of in vitro inhibition of the pineal AAA activity by melatonin. Acute subcutaneous injection of low doses (25-50 mg/kg) THBC harmaline, desipramine and protriptyline markedly inhibited the rat pineal AAA activity but at higher doses (75-100 mg/kg) the inhibition was reduced. On the contrary, RO4-4602 (200-800 mg/kg) greatly enhanced (1.5-2.3 fold) the enzyme activity, inversely proportional to the doses given. In view of the differential effects of these drugs on the brain and pineal AAA, it seems unlikely that they would be the same enzyme.

Amidohydrolases↗
PubMed1983

Differential-reinforcement-of-low-rate 72-second schedule: selective effects of antidepressant drugs.

The effects of antidepressant drugs in rats responding under a differential-reinforcement-of-low-rate 72-sec schedule were assessed. Seven clinically used tricyclic antidepressant drugs (imipramine, desipramine, chlorimipramine, protriptyline, nortriptyline, amitriptyline and doxepin), two atypical antidepressants (iprindole and mianserin) and a monoamine oxidase inhibitor (tranylcypromine) dose-dependently reduced response rate and increased reinforcement rate. Nomifensine, an atypical antidepressant which has been reported to have psychomotor stimulant properties and abuse potential, increased response rate and decreased reinforcement rate. Chlorpromazine, an antipsychotic agent, and diphenhydramine, an antihistamine, have been reported to produce effects similar to antidepressants in several behavioral tests, but neither of these drugs mimicked the actions of antidepressants on responding under a differential-reinforcement-of-low-rate 72-sec schedule. Chlorpromazine decreased response rate but did not increase reinforcement rate. Diphenhydramine did not have consistent effects but tended to decrease reinforcement rate. These findings suggest that behavior maintained by the differential-reinforcement-of-low-rate schedule may be selectively affected by antidepressants that have no psychomotor stimulant properties.

Animals↗
PubMed1980

[Metabolism and blood levels study of antidepressants: a rationale of their therapeutical use (author's transl)].

The authors show with some examples the interest of pharmacokinetics for the optimization of the therapeutical use of antidepressive agents. They give some indications about bioavailabilty, metabolism and half-life of these compounds and note the importance of the individual variations. They also analyze the studies on the possible relations between the clinical response and the steady-state plasma levels of the unchanged drug and/or its active metabolite. The relation between these two parameters would be linear for imipramine, amitriptyline, clomipramine, doxepine, dibenzepine, and curvilinear for nortriptyline, desipramine, protriptyline, maprotiline and mianserine, especially in endogenous depression. From a previous pharmacokinetic study calculations allow to predict the steady-state plasma concentrations. The question of the side effects and drug interactions is considered.

Antidepressive Agents↗
PubMed1982

Sample preparation and liquid-chromatographic analysis for tricyclic antidepressants in serum.

We report two separate sample-preparation procedures and a "high-pressure" liquid-chromatographic method for quantitating nine tricyclic antidepressant drugs: trimipramine, doxepin, amitriptyline, imipramine, desmethyldoxepin, nortriptyline, desipramine, maprotiline, and protriptyline. The drugs are extracted from 1 mL of serum by a single manual hexane extraction or by using DuPont's PREP I Automated Sample Processor. The drugs from either process are chromatographed on a mu-Bondapak-CN column with a mobile phase of acetonitrile/methanol/Na2HPO4, 5 mmol/L (60/15/25 by vol), pH 7.0, at a flow rate of 2.0 mL/min. Absorbance at 254 nm is linear with drug concentration from 25 to 1000 mg/L for each drug. With the manual extraction procedure the detection limit was 10 mg/L, absolute recovery 20-44%, within-run precision (CV) 10.1%, and run-to-run precision 11.1%. The performance of automated sample extraction was better, with a detection limit of 5 mg/l, absolute recovery 72-97%, within-run precision 6.1%, and run-to-run precision 6.6%.

Antidepressive Agents, Tricyclic↗