Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Protriptyline”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 271 records · Page 15Linked to original sources
PubMed2002

Effects of antidepressants in rats trained to discriminate centrally administered isoproterenol.

Previous work has shown that the discriminative stimulus effects of centrally administered isoproterenol are mediated primarily via beta1-adrenergic receptors. In the present study, this model was used to investigate the ability of antidepressant drugs displaying various pharmacological profiles to stimulate beta1-adrenergic receptors in vivo; this was assessed by determining whether they substituted for the discriminative stimulus effects of isoproterenol. Rats were trained to discriminate centrally administered isoproterenol (10 microg i.c.v.) from artificial cerebral spinal fluid using a water-reinforced, two-lever operant task (fixed ratio 10 schedule). After acquisition of the discrimination, drugs were tested for substitution (i.p.). The tricyclic antidepressants protriptyline and desipramine, the norepinephrine uptake inhibitor nisoxetine, the monoamine oxidase inhibitor phenelzine, and the atypical antidepressants bupropion, mirtazapine, and venlafaxine all produced greater than 90% isoproterenol-appropriate responding. The serotonin uptake inhibitor fluoxetine, the atypical antidepressants buspirone and trazodone, and the novel, putative antidepressants N(G)-nitro-L-arginine and N-acetyl-L-tryptophan 3,5-bis benzyl ester failed to substitute for isoproterenol at the dose ranges tested. Antagonism studies carried out with betaxolol for those drugs that fully generalized to isoproterenol's cue verified mediation by beta1-adrenergic receptors. The present results indicate that drugs with noradrenergic activity generalize to isoproterenol's discriminative stimulus. Although this suggests a role for central beta1-adrenergic receptors in the mechanism of action of certain antidepressant drugs, it does not seem that stimulation of these receptors is an effect shared by antidepressants from all pharmacological classes.

Animals↗
PubMed1966

Prevention of the emergence of drug resistance in bacteria by acridines, phenothiazines, and dibenzocycloheptenes.

It has been found that, like Atabrine, the phenothiazine tranquilizers promazine, chlorpromazine, promethazine, levopromethazine, and Stelazine; the antidepressants (dibenz-azepine and dibenzocycloheptene derivatives) Tofranil, Pertofrane, cyclobenzaprine, Elavil, protriptyline, and 3-chlorodibenzocycloheptene; and the acridine derivatives acridine orange, acriflavin, SKF no. 16214-A2, SKF no. 13231-A2, SKF no. 9200, and SKF no. 9836 are all to a greater or lesser extent than Atabrine, effective in preventing the emergence of resistant strains of Staphylococcus aureus and Escherichia coli in the presence of streptomycin, sulfathiazole, or chloramphenicol. The antimalarials chloroquine and hydroxychloroquine were also studied and found to be ineffective. The medical significance of these findings is discussed, as well as the effect of the structural variations of these compounds on their relative activities.

Journal Article↗
PubMed1987

Fatal toxicity of antidepressant drugs in overdose.

A fatal toxicity index (deaths per million National Health Service prescriptions) was calculated for antidepressant drugs on sale during the years 1975-84 in England, Wales, and Scotland. The tricyclic drugs introduced before 1970 had a higher index than the mean for all the drugs studied (p less than 0.001). In this group the toxicity of amitriptyline, dibenzepin, desipramine, and dothiepin was significantly higher, while that of clomipramine, imipramine, iprindole, protriptyline, and trimipramine was lower. The monoamine oxidase inhibitors had intermediate toxicity, and the antidepressants introduced since 1973, considered as a group, had significantly lower toxicity than the mean (p less than 0.001). Of these newer drugs, maprotiline had a fatal toxicity index similar to that of the older tricyclic antidepressants, while the other newly introduced drugs had lower toxicity indices, with those for mianserin, nomifensine, trazodone, and viloxazine reaching significance. Provided that these drugs are equally effective clinically, serious consideration should be given to prescribing antidepressants with a lower fatal toxicity.

Amitriptyline↗
PubMed1994

Role of respiratory sleep disorders in the pathogenesis of nocturnal angina and arrhythmias.

This report documents how respiratory sleep disorders can adversely effect ischaemic heart disease. Three male patients (aged 60-67 years) with proven ischaemic heart disease are described. They illustrate a spectrum of nocturnal cardiac dysfunction, two with nocturnal angina and one with nocturnal arrhythmias. Full sleep studies were performed in a dedicated sleep laboratory on all patients, and one patient had 48 hours of continuous Holter monitoring. Two patients were found to have obstructive sleep apnoea with apnoea/hypopnoea indices of 57 and 36 per hour, respectively, the former with nocturnal arrhythmias and the latter with nocturnal angina. In both cases, nasal continuous positive airways pressure successfully treated the sleep apnoea, with an associated improvement in nocturnal arrhythmias and angina. The third patient who presented with nocturnal angina, did not demonstrate obstructive sleep apnoea (apnoea/hypopnoea index = 7.2) but had significant oxygen desaturation during rapid eye movement (REM) sleep. This patient responded to a combination of nocturnal oxygen and protriptyline, an agent known to suppress REM sleep, and had no further nocturnal angina. All patients were considered to be an optimum cardiac medication and successful symptom resolution only occurred with the addition of specific therapy aimed at their sleep-related respiratory problem. We conclude that all patients with nocturnal angina or arrhythmias should have respiratory sleep abnormalities considered in their assessment.

Aged↗
PubMed2000

Transtracheal air in the treatment of obstructive sleep apnoea hypopnoea syndrome.

A 49 year old woman with typical obstructive sleep apnoea hypopnoea syndrome underwent an unsuccessful trial with continuous positive airway pressure (CPAP) followed by uvulopalatopharyngoplasty with septorhinoplasty, treatment with protriptyline, and a second CPAP trial that was abandoned. Transtracheal air was then given and normalised sleep and breathing at a flow rate of 5 l/min. A sustained clinical improvement was observed at follow up visits. Transtracheal air could represent a simple and effective alternative to tracheotomy in patients with obstructive sleep apnoea hypopnoea syndrome in whom conventional treatments fail.

Female↗
PubMed1985

Genesis of rhythmic respiratory activity in pons independent of medulla.

We hypothesized that rhythmic respiratory-related activity could be generated in pons independent of medullary mechanisms. In decerebrate, cerebellectomized, vagotomized, paralyzed, and ventilated cats, we recorded efferent activities of the phrenic nerve and mylohyoid branch of the trigeminal nerve. Following transections of the brain stem at the pontomedullary junction, the phrenic and trigeminal nerves discharged with independent rhythms. Spontaneous trigeminal discharges eventually ceased but were reestablished after strychnine, doxapram, and/or protriptyline were administered. In some animals having no spontaneous trigeminal discharges after transection, these discharges appeared, with a rhythm different from the phrenic, following administration of these agents. In other cats having no transections between pons and medulla, these pharmacological agents induced trigeminal and phrenic discharges after kainic acid had been injected into the entire dorsal and ventral medullary respiratory nuclei. Phrenic and trigeminal discharges were linked, indicating survival of bulbospinal neurons or presence of pontospinal units. We conclude that rhythms, similar to respiratory rhythm, can occur by mechanisms in isolated pons. Such mechanisms are hypothesized to be within the pneumotaxic center and may underlie the neurogenesis of eupnea.

Action Potentials↗
PubMed1988

Respiratory neural activities after caudal-to-rostral ablation of medullary regions.

The purpose is to assess the importance of medullary mechanisms for the neurogenesis of eupnea. Cats that were used were decerebrate, cerebellectomized, vagotomized, paralyzed, and ventilated. Activities of the phrenic, facial, and mylohyoid nerves were monitored. Progressive caudal-to-rostral transections of the spinal cord and medulla were performed. Phrenic activity was eliminated by C1 spinal transections. Only modest changes in facial and mylohyoid activities resulted from transections as far rostral as the level of the dorsal respiratory nucleus. Rhythmic discharges ceased on transections at the pontomedullary junction. However, rhythmic mylohyoid discharges were maintained if protriptyline and strychnine were administered before and during the transection. In other studies rhythmic phrenic, facial, and mylohyoid discharges continued, albeit with an altered rhythm, after destruction of neurons in the dorsal respiratory nucleus by kainic acid. We conclude that caudal medullary mechanisms do not play an essential role in the neurogenesis of breathing movements. Rather, structures in rostral medulla and pons appear necessary for sustaining eupneic neural activities. The concept of multiple brain stem sites for ventilatory neurogenesis is discussed.

Animals↗
PubMed1987

Screening of drugs for thermogenic anti-obesity properties: antidepressants.

Twelve antidepressant drugs, currently in clinical use, were screened for thermogenic properties on the basis of their ability to stimulate the activity of the sympathetic nervous system via an inhibitory effect on noradrenaline reuptake into the sympathetic neurons. Drug screening was carried out on mice made obese by hypothalamic lesioning using monosodium glutamate. Preliminary experiments, based on changes in body weight and food intake in response to increased doses of the drugs, indicate that most of the twelve antidepressants possess thermogenic potential. In particular, butriptyline, protriptyline and nortriptyline were most effective in causing marked losses in body weight without altering the food intake of the mice. The potent anti-obesity thermogenic properties of these three antidepressants were confirmed during a 10-week energy balance study involving measurements of energy expenditure over the entire period by the comparative carcass method, as well as by measurement of 24 h oxygen consumption. These studies indicate that the methodology employed in the preliminary screening is valid for identifying drugs with thermogenic potential, and demonstrate that many antidepressants currently in clinical use have marked thermogenic properties, and could therefore influence the nutritional status of patients under drug therapy.

Animals↗
PubMed1987

Long-term cardiopulmonary sequelae in patients with sleep apnea and chronic lung disease.

Both obstructive sleep apnea and chronic lung disease can be associated with intermittent or chronic hypoxemia leading to pulmonary hypertension and cor pulmonale. When these problems coexist, it is possible that the cardiopulmonary effects are additive. We hypothesized that hemodynamic disturbances in patients with apnea and lung disease would be more severe than in those with apnea alone, and that hemodynamic improvement should follow apnea cure, but perhaps at a slower rate than in those with apnea alone. To test these hypotheses, we prospectively followed 24 patients with sleep apnea syndrome. They were divided into 3 nonrandomized groups. Nineteen patients had both apnea and lung disease. Nine of these agreed to curative tracheostomy (Group 1). The other 10 subjects (Group 2) refused tracheostomy but accepted noncurative therapies, including nocturnal oxygen (n = 9), uvulopalatopharyngoplasty (n = 2), and protriptyline (n = 4). Five subjects with apnea but without clinically obvious lung disease received tracheostomies (Group 3). Subjects were followed at yearly intervals (mean follow-up, 27.2 months) with radionuclide motion studies and, in 15 of 24 who consented, right heart catheterization. The 3 groups did not vary with respect to age, percent ideal weight, or severity of apnea symptoms. The severity of right-sided hemodynamic dysfunction in the group with apnea but no obvious lung disease was less than that in the 2 groups with lung disease. A substantial decrease in pulmonary artery pressure (p = 0.056) and significant improvement in right ventricular ejection fraction occurred in the tracheostomized group with both apnea and lung disease. Pulmonary vascular resistance decreased in both groups receiving tracheostomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic Disease↗
PubMed1994

Epilepsy and sleep apnea syndrome.

We identified seven patients with refractory partial epilepsy and sleep apnea. Treatment of the sleep apnea with nasal continuous positive airway pressure (CPAP), protriptyline, trazodone, acetazolamide, or tracheostomy reduced seizure frequency and severity in six patients. Success with CPAP depended largely on compliance. Four of five patients had a clear reduction in seizure frequency with the use of CPAP. Sleep apnea may exacerbate epilepsy by causing sleep disruption and deprivation, hypoxemia, and decreased cerebral blood flow. In epilepsy patients with risk factors (eg, obesity) or markers (eg, habitual snoring, daytime somnolence) for sleep apnea, a careful sleep history should be elicited and a polysomnogram obtained when indicated. Treatment of the sleep disorder can improve seizure control.

Adult↗
PubMed1984

Clinical conference in pulmonary disease. Factors influencing upper airway closure.

The factors which produce closure of the upper airway (UAW) in patients with the sleep apnea syndrome are still poorly understood. A distinction should be made between the factors which induce closure and those which reopen the UAW. Neurologic factors include arousal phenomena, the magnitude and timing of various motor outputs, and postsynaptic inhibition. Mechanical factors include the anatomy of the UAW, especially that above the tongue, the position of the neck and jaw, and mucosal adherence once occlusion has occurred. Muscle factors include the type of myosin isozyme, the forces generated by the large number of UAW muscles and the diaphragm, and the possibility of high-frequency fatigue occurring during occlusion. Hypoxia and acidosis probably play a critical role in making the UAW less stable. Currently, the best method to prevent UAW closure is by nasal CPAP. Patients with life-threatening arrhythmias due to sleep apnea should have a tracheostomy. The role of drugs is controversial. Respiratory or muscle stimulants should probably be avoided; oxygen, medroxyprogesterone, and protriptyline may be useful adjuncts.

Humans↗
PubMed2004

Current use of selective serotonin reuptake inhibitors and risk of acute myocardial infarction.

BACKGROUND: It has been suggested that increased platelet activation increases the risk of acute myocardial infarction (AMI) in patients with depression. Selective serotonin reuptake inhibitors (SSRIs) may attenuate platelet activation by serotonin depletion in platelets. Observational studies have shown discrepant results of AMI risk associated with the use of SSRIs. OBJECTIVE: The aim of this study was to evaluate the association of exposure to different groups of antidepressants, including SSRIs, and the risk of AMI. The study also assessed in more detail the influence of timing of the exposure to antidepressants in a general adult population (<90 years of age), with or without diagnosed risk factors for AMI. STUDY DESIGN/METHODS: We conducted a population-based case-control analysis on the UK General Practice Research Database (GPRD). The study included 8688 patients (<90 years of age), with a first-time AMI between 1995 and 2001, and 33 923 controls, who were matched by age, sex, calendar time, and general practice. Conditional logistic regression was used to estimate odds ratios (ORs). RESULTS: Current use of an antidepressant was defined as a supply of the last prescription for an antidepressant that lasted up to the index date or beyond. Recent past use was defined as a supply of the last prescription for an antidepressant that ended 1-29 days before the index date. SSRIs investigated were citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline and venlafaxine. Non-SSRIs investigated were amitriptyline, clomipramine, dosulepin, doxepin, imipramine, lofepramine, nefazodone, trazodone and trimipramine. Other antidepressants included were amoxapine, desipramine, lithium, maprotiline, mianserin, moclobemide, nortriptyline and protriptyline. Adjusted ORs (with 95% CI) for the current use of SSRIs, non-SSRIs, or other antidepressants, compared with non-use of antidepressants, were 0.63 (95% CI 0.43, 0.91; p=0.02), 0.92 (95% CI 0.77, 1.09; p=0.32) and 0.59 (95% CI 0.29, 1.20; p=0.14), respectively. The adjusted OR of recent past use of SSRIs compared with non-use of SSRIs was 1.42 (95% CI 1.02, 1.97; p=0.04). CONCLUSION: The present analysis provides further evidence that the current use of SSRIs is associated with a slightly decreased risk for AMI.

Age Distribution↗
PubMed2004

Pharmacotherapies for obstructive sleep apnoea: where are we now?

Obstructive sleep apnoea (OSA) is common, causes considerable morbidity and probably contributes to mortality particularly through associated cardiovascular disease. The physical therapy of continuous positive airway pressure (CPAP) is extremely effective in the majority of patients but most patients would prefer an alternative. Intuitively, OSA should be amenable to pharmacotherapy. The upper airway of affected individuals can be narrowed but is patent during wakefulness. Collapse of the airway during sleep occurs when negative intra-luminal pressure generated by inspiratory effort exceeds the tone of the upper airway dilators. This mismatch may be in part due to respiratory drive instability but the state-dependent fall in drive to the airway dilator muscles is the biggest factor in most patients. Various drugs have been investigated as treatment for OSA. Acetazolamide, theophylline, nicotine, opioid antagonists and medroxyprogesterone have been used to increase respiratory drive. Clonidine has been tested with the aim of reducing rapid eye movement sleep when OSA is often most severe. Various antidepressants have been used to suppress rapid eye movement sleep and to preferentially activate the upper airway dilators. The drug trials have often been of poor design and none has included more than a few patients. Most of the drugs have been found to be ineffective and those that have worked for some patients (acetazolamide and protriptyline) have produced intolerable adverse effects. There have been recent advances in the understanding of the neurotransmitters involved in the control of sleep and the upper airway motor neurones, offering the possibility of novel approaches to the drug treatment of OSA for those patients who cannot tolerate or do not benefit from CPAP. It seems likely that a better understanding of the mechanisms of OSA in individual patients and tailoring of drug therapy will be the way forward.

Clinical Trials as Topic↗
PubMed1997

Evaluation of a colloidal metal immunoassay device for the detection of tricyclic antidepressants in urine.

BACKGROUND: The sensitivity and selectivity of a colloidal metal immunoassay device (Triage Plus TCA) which is designed for the rapid detection of tricyclic antidepressant drugs in urine at a total tricyclic antidepressant concentration of 1000 ng/mL or greater were evaluated. METHODS: The sensitivity of the Triage Plus assay was determined by adding known amounts of amitriptyline, nortriptyline, imipramine, desipramine, doxepin and desmethyl-doxepin to drug free urine. The selectivity of the assay was determined by adding known concentrations of 32 drugs or drug metabolites commonly encountered in emergency department admissions to drug free urine. Triage Plus results from clinical urine specimens containing either amitriptyline, nortriptyline, imipramine, desipramine, doxepin and desmethyl-doxepin were compared to those obtained with thin layer chromatography and high performance liquid chromatography. RESULTS: Triage Plus yielded a positive response to gravimetrically prepared urines of tricyclic antidepressant at the stated cut-off value (1,000 ng/mL), and at 80% (800 ng/mL) and 50% (500 ng/mL) of the cut-off with amitriptyline, nortriptyline, imipramine, desipramine and doxepin. Other tricyclic antidepressant drugs, clomipramine and protriptyline were positive at 1000 ng/mL. Significant cross-reactivity was observed only with cyclobenzaprine at 1000 ng/mL. No significant cross reactivity was found at 1.0 g/L for 32 drugs commonly encountered in emergency department admissions. A 95% (70/74) agreement of positive tricyclic antidepressant results was observed between Triage Plus and thin layer chromatography. Discordant urines were found by high performance liquid chromatography to contain tricyclic antidepressant concentrations below the cut-off value of the colloidal metal assay. CONCLUSION: Triage Plus was found to be an accurate device for the detection of tricyclic antidepressants in urine at the stated cut-off value of 1000 ng/mL tricyclic antidepressant. With the exception of cyclobenzaprine, significant cross-reactivity was not observed with other drugs commonly encountered in emergency department admissions.

Antidepressive Agents, Tricyclic↗
PubMed1975

The effect of beta-phenylethylamine on temperature in mice and its possible mechanisms of action.

Beta-phenylethylamine on injection into mice (100 mg/kg i.p.) produces a marked hyperthermia which is followed by a prolonged hypothermia. The hyperthermic response was studied in this report. The hyperthermic response was inhibited by p-chlorophenylalanine, methysergide, cyproheptadine, alpha-methyl-tyrosine, propranolol, practolol, phenoxybenzamine, phentolamine, haloperidol, pimozide, protriptyline and desipramine. Lysergic acid diethylamide potentiated the response, while p-chloroamphetamine was without effect. While FLA-63 potentiated the response, disulfiram and reserpine were ineffective in preventing the hyperthermia. Nicotinic acid and prostaglandin E1 did not prevent PE induced hyperthermia. It was concluded from these results that PE induced hyperthermia in mice is blocked by agents that reduce the effective concentration of either DA or 5-HT in the central nervous system (by either synthesis inhibitors or receptor blockers). The involvement with catecholaminergic neurons at least was postulated to be a result of PE induced release of DA from DA neurons.

Animals↗
PubMed1976

Gas-chromatographic analysis for therapeutic concentrations of amitriptyline and nortriptyline in plasma, with use of a nitrogen detector.

We describe a gas-chromatographic procedure for the simultaneous determination of amitriptyline and its active metabolite, nortriptyline, in therapeutic concentrations in human plasma, with use of a nitrogen detector. Both drugs are extracted at pH 10.5 into hexane/isoamyl alcohol, back-extracted into dilute HCl, and re-extracted into hexane/isoamyl alcohol after alkalinization of the HCl. The solvent is evaporated and the residue gas-chromatographed. Protriptyline is used as the internal standard. As little as 5 mug of amitriptyline or nortriptyline can be detected per liter of plasma. The coefficients of variation, for a concentration of 200 mug/liter, are 4.6% and 4.3% within-day and 8.6% and 3.4% day-to-day for amitriptyline and nortriptyline, respectively. The procedure was applied to patients receiving therapeutic doses of both drugs and also to patients who had taken overdoses of amitriptyline.

Amitriptyline↗
PubMed1992

Suicide and fatal antidepressant poisoning.

OBJECTIVE: To compare the fatal toxicities of antidepressant drugs in England, Scotland and Wales 1985-1989. METHODS: Epidemiological retrospective study using Department of Health prescription data and mortality data from the Office of Population Censuses and Surveys, and the Registrar General for Scotland, for the years 1974-1989. The fatal toxicity index (FTI) of groups of drugs and individual drugs was compared with the FTI for all antidepressant drugs for the years 1985-1989. RESULTS: Of 3,604 single antidepressant deaths between 1975 and 1989, the majority (70.95%) were from amitriptyline or dothiepin. The mean FTI for all drugs for the years 1985-1989 was 35.6; the FTIs for dothiepin, amitriptyline, nortriptyline and tranylcypromine were significantly higher than the mean of all, while those for clomipramine, lofepramine, fluvoxamine, trimipramine, maprotiline, trazodone, mianserin, protriptyline, isocarboxazid and phenelzine were lower. The FTI for the older tricyclic drugs was higher at 43.03 (p < 0.001). The FTI for the monoamine oxidase inhibitors, of 27.03 (p = 0.045), and for all drugs introduced after 1973, of 5.32 (p < 0.001), were each significantly lower than the mean of all drugs. CONCLUSIONS: Overdose deaths from antidepressants have not decreased over the last 15 years. A trend away from prescribing drugs with a higher fatal toxicity index in favour of those with a lower index, would reduce the number of deaths from antidepressant poisoning.

Acute Disease↗
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↗