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PubMedDate not supplied

Selective determination of amitriptyline and nortriptyline in human plasma by HPLC with ultraviolet and particle beam mass spectrometry.

A selective, sensitive, and reliable method was devised to determine concentrations of amitriptyline and its major metabolite, nortriptyline, in human plasma using high-performance liquid chromatography (HPLC) combined with UV and particle beam mass spectrometry (PBMS). Amitriptyline and nortriptyline were effectively extracted in a three-step solvent extraction procedure. Imipramine was used as the internal standard (IS). Amitriptyline, nortriptyline, and the IS were clearly separated by HPLC on a silica column with the mobile phase of acetonitrile-0.1 M ammonium acetate (94:6, v/v). The calibration curves were linear in the concentration range of 10-1000 ng/g for both compounds with UV and PBMS detections. The lower limits of detection were 5 ng/g for amitriptyline and 10 ng/g for nortriptyline with UV detection and 2 ng/g for amitriptyline and 5 ng/g for nortriptyline with PBMS detection. The absolute recoveries were 58% for amitriptyline and 47% for nortriptyline at a concentration of 50 ng/g. This method proved most useful in accurately identifying amitriptyline and nortriptyline in tissues from an autopsied individual.

Acetates↗
PubMedDate not supplied

Interpretation of blood and tissue concentrations in fatal self-ingested overdose involving amitriptyline: an update (1978-1979).

Thirty-two cases of fatal self-ingested overdose involving amitriptyline were studied over the two-year period 1978 to 1979. The average decedent was a 44-year-old woman who ingested amitriptyline and at least one other drug (usually ethanol, diazepam, propoxyphene, or codeine). The mean concentrations of amitriptyline and nortriptyline were significantly higher in liver than in myocardium, and they were significantly higher in myocardium than in blood. In addition, concentrations in these tissues showed significant correlation with each other. The mean tissue concentrations of amitriptyline and nortriptyline in this series of overdoses were significantly greater than those in fourteen other decedents whose deaths were not due to drug overdose but involved amitriptyline as an incidental finding. The mean ratio of amitriptyline to nortriptyline in each tissue was also significantly higher in overdose than those in the corresponding tissues of the non-overdose group, suggesting that the former ingestions were more acute. The estimated survival times showed no significant correlation with tissue concentrations of either amitriptyline or nortriptyline.

Adult↗
PubMed1989

Pharmacokinetics of lofepramine and amitriptyline in elderly healthy subjects.

Pharmacokinetics of 3 doses (70 mg, 105 mg and 140 mg) of lofepramine were compared with amitriptyline (50 mg) in 6 healthy drug free elderly subjects aged between 65 and 72 years. Pharmacokinetics of lofepramine in the elderly appear to be similar to young adults as published before. Peak plasma lofepramine and amitriptyline concentrations were achieved at about 1 h and 3 h of dosing respectively. Elimination half-life of lofepramine was 2.5 h and that of amitriptyline was 31 h. A 24-fold inter-individual variation in peak plasma lofepramine concentrations was observed, but amitriptyline levels in plasma showed less variation. Pharmacokinetic parameters of amitriptyline were comparable to other published studies involving elderly people. Compared to placebo and lofepramine, amitriptyline produced drowsiness and dry mouth, reduced salivary volume and increased movement reaction time. These effects correlated with the plasma amitriptyline levels.

Aged↗
PubMed1992

Paroxetine in the treatment of elderly depressed patients in general practice: a double-blind comparison with amitriptyline.

A total of 101 patients entered a double-blind, parallel-group study in general practice, comparing the efficacy and tolerability of paroxetine and amitriptyline in elderly depressed patients. All patients received placebo for 1 week followed by active therapy for a total of 6 weeks. Medication was randomly allocated, two-thirds of the patients took paroxetine (20 mg daily) and one-third received amitriptyline (50 mg daily); this dose was increased to 30 mg and 100 mg, respectively, after 1 week. Of the patients who entered the placebo run-in, 90 took active treatment and were evaluable on an intention-to-treat basis (56 paroxetine, 32 amitriptyline). The mean age of the patients was 72 years. Significant reductions in Hamilton Depression Rating Scale (HAMD) from baseline to the end of treatment were seen for both groups (p < 0.01), with no difference between treatments. The HAMD score was reduced by half, or more, for 76% of patients taking paroxetine and 86% taking amitriptyline. Significant improvement was observed in the investigators' Clinical Global Impression (CGI) score for 57% of patients taking paroxetine and 52% on amitriptyline. Improvements after treatment were also observed in the Leeds Sleep Evaluation Questionnaire (LSEQ) scores. Significantly fewer patients taking paroxetine reported adverse events (34% vs 63% taking amitriptyline, p = 0.02). Those taking paroxetine experienced significantly fewer anticholinergic side effects (7% vs 25% taking amitriptyline, p = 0.04). Overall, this study confirmed the effectiveness of paroxetine as an antidepressant drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1999

Fluoxetine versus amitriptyline in the treatment of major depression with associated anxiety (anxious depression): a double-blind comparison.

Although common in clinical settings, major depressive disorder with associated anxious symptoms ('anxious depression') has not been well studied in antidepressant clinical trials. The aim of this study was to compare the effects of fluoxetine versus amitriptyline in this group of patients. After a single-blind placebo run-in period of 2 weeks, patients were treated on a double-blind basis with fluoxetine or amitriptyline for 8 weeks. Assessment instruments included: 21-item Hamilton Rating Scale for Depression, Hamilton Rating Scale for Anxiety, Clinical Global Impressions, Raskin Depression Scale and Covi Anxiety Scale. A total of 157 patients were randomized to either fluoxetine or amitriptyline. Fluoxetine was given at a fixed dose of 20 mg/day and amitriptyline was given in a range of 50-250 mg/day (mean of 138.1 mg/day). Fluoxetine was comparable to amitriptyline in all efficacy measures except the HAMD sleep factor. Unwanted effects were more frequent and more severe in the amitriptyline-treated patients. Fluoxetine was comparably efficacious to amitriptyline in the treatment of major depression with associated anxiety. Since fluoxetine was far better tolerated, it is a promising alternative for this frequent and disabling condition.

Adult↗
PubMed1990

Comparative effects of antidepressants, amitriptyline, and maprotiline on intraventricular conduction, effective refractory period, and incidence of ventricular arrhythmias induced by programmed stimulation in dog hearts after myocardial infarction.

The effects of amitriptyline and maprotiline, standard tricyclic and tetracyclic antidepressants, on intraventricular conduction, the effective refractory period (ERP), and the incidence of ventricular arrhythmias induced by programmed stimulation were studied and compared in dog hearts after myocardial infarction. Amitriptyline at doses of 1-3 mg/kg significantly slowed ventricular conduction of the infarcted zones in a frequency-dependent and dose-dependent manner. Amitriptyline at doses of 2 and 3 mg/kg slowed conduction slightly in normal zones. The ERP was prolonged by amitriptyline at a dose of 2 mg/kg. Amitriptyline increased the incidence of ventricular arrhythmias induced by programmed stimulation. Maprotiline at doses of 1-3 mg/kg slowed conduction in infarcted zones to a lesser extent as compared with amitriptyline, although severely depressed conduction in the infarcted zone was obviously slowed by maprotiline. Maprotiline did not increase the incidence of ventricular arrhythmias significantly. From the present results, maprotiline appears to have less cardiac toxicity than amitriptyline, although maprotiline produces a slight decrease in conduction of infarcted zones.

Action Potentials↗
PubMed1983

Effects of amitriptyline, desipramine and mianserin on noradrenergic transmission in the rat isolated right ventricle.

The effects of amitriptyline, desipramine and mianserin on the accumulation of radioactivity from [3H]-noradrenaline, and on the subsequent spontaneous and field stimulation-evoked outflow of radioactivity have been investigated in the rat isolated right ventricle. In addition the effect of these agents on contractions produced by isoprenaline or by field stimulation are reported. Amitriptyline, desipramine (both at greater than or equal to 10(-8) M) and mianserin at greater than or equal to 10(-7) M inhibited the accumulation of radioactivity from [3H]-noradrenaline. The decline in the spontaneous outflow of radioactivity, following loading of the tissue with [3H]-noradrenaline, was not altered by amitriptyline, desipramine or mianserin. Rauwolscine, amitriptyline, desipramine and mianserin (all at 10(-6) M) reduced or reversed the decline in outflow of radioactivity evoked by field stimulation at 5 Hz. Desipramine had no additional effects in the presence of cocaine (10(-5) M) and amitriptyline and mianserin had no further effect in the presence of cocaine and rauwolscine. The effect of desipramine probably represents inhibition of neuronal uptake and that of amitriptyline and mianserin blockade of neuronal uptake and prejunctional alpha 2-adrenoreceptors. The rate of beating in the presence of isoprenaline (10(-6) M) was reduced by amitriptyline (10(-7) M), desipramine (10(-6) M) and mianserin (10(-7)--10(-6) M). Higher concentrations of the antidepressants greatly reduced or abolished the rate and force of beating in the presence of isoprenaline.(ABSTRACT TRUNCATED AT 250 WORDS)

Amitriptyline↗
PubMed1979

The relative toxicity of amitriptyline, imipramine, maprotiline and mianserin in rabbits in vivo.

1. Conscious or barbiturate-anaesthetized rabbits were slowly infused intravenously with solutions of amitriptyline, imipramine, maprotiline or mianserin, usually until death occurred. 2. Amitriptyline produced death at the lowest dose, imipramine and maprotiline were intermediate while much higher doses of mianserin were required. 3. Convulsions were induced by the antidepressants in all conscious rabbits and the order of potency of the drugs in producing this effect was amitriptyline greater than or equal to imipramine greater than maprotiline greater than mianserin. 4. All four drugs produced a reduction in heart rate and blood pressure in the anaesthetized rabbits and the order of potency in this respect was amitriptyline greater than imipramine greater than maprotiline greater than mianserin. 5. All four drugs produced significant changes in the ECG compared with control rabbits. The P-R interval was lengthened (potency order amitriptyline greater than imipramine greater than or equal to maprotiline greater than mianserin) and the QRS complex was widened (potency order amitriptyline greater than imipramine greater than or equal to maprotiline greater than mianserin). 7. It is concluded that all four drugs show the toxic effects classically associated with tricyclic antidepressants but the relative toxicity amongst these agents varies considerably and is in the order amitriptyline greater than imipramine greater than maprotiline greater than mianserin.

Amitriptyline↗
PubMed1995

Potent block of potassium currents in rat isolated sympathetic neurones by the uncharged form of amitriptyline and related tricyclic compounds.

1. The block of K+ currents by amitriptyline and the related tricyclic compounds cyproheptadine and dizocilpine was studied in dissociated rat sympathetic neurones by whole-cell voltage-clamp recording. 2. Cyproheptadine (30 microM) inhibited the delayed-rectifier current (Kv) by 92% and the transient current (KA) by 43%. For inhibition of Kv, cyproheptaidine had a KD of 2.2 microM. Dizocilpine (30 microM) inhibited Kv by 26% and KA by 22%. The stereoisomers of dizocilpine were equally potent at blocking Kv and KA. 3. Amitriptyline, a weak base, was significantly more effective in blocking Kv at pH 9.4 (KD = 0.46 microM) where the ratio of charged to uncharged drug was 50:50 compared with pH 7.4 (KD = 11.9 microM) where the ratio was 99:1. 4. N-methylamitriptyline (10 microM), the permanently charged analogue of amitriptyline, inhibited Kv by only 2% whereas in the same cells amitriptyline (10 microM) inhibited Kv by 36%. 5. Neither amitriptyline nor N-methylamitriptyline had a detectable effect on Kv when added to the intracellular solution. 6. It is concluded that the uncharged form of amitriptyline is approximately one hundred times more potent in blocking Kv than the charged form. However, this does not seem to be due to uncharged amitriptyline having better access to an intracellular binding site.

Amitriptyline↗
PubMed1989

Why do amitriptyline and dothiepin appear to be so dangerous in overdose?

Data from different analyses of reported deaths from overdose with antidepressants in the U.K. reveal that amitriptyline and dothiepin are the antidepressants most likely to be associated with death from overdose. All widely used tricyclic antidepressants (TCAs) except clomipramine and lofepramine appear to be dangerous in overdose, whereas the newer antidepressants such as mianserin, trazodone, viloxazine and the TCA lofepramine appear to be relatively safe. The toxicity of amitriptyline and dothiepin appears to be greater than all antidepressants including other TCAs and it is important to try to understand why. A number of explanations will be considered: 1. Dothiepin and amitriptyline may be inherently more toxic than other TCAs. 2. Dothiepin and amitriptyline may induce suicide more than other antidepressants. It is assumed that antidepressants are neutral with regard to inducing suicide but this may not be true. There is, for example, evidence that alprazolam and other benzodiazepines induce suicidal behaviour. 3. Amitriptyline and dothiepin are often presented in subtherapeutic and ineffective doses and it is possible that increased suicides may result from inadequately treated depression. 4. There may be a selective overreporting of deaths with amitriptyline and dothiepin. 5. Amitriptyline and prothiaden may be selectively given to the suicide prone on the mistaken assumption that they are safe.

Amitriptyline↗
PubMed2005

Amitriptyline reduces rectal pain related activation of the anterior cingulate cortex in patients with irritable bowel syndrome.

BACKGROUND AND AIMS: Irritable bowel syndrome (IBS) is a disorder of intestinal hypersensitivity and altered motility, exacerbated by stress. Functional magnetic resonance imaging (fMRI) during painful rectal distension in IBS has demonstrated greater activation of the anterior cingulate cortex (ACC), an area relevant to pain and emotions. Tricyclic antidepressants are effective for IBS. The aim of this study was to determine if low dose amitriptyline reduces ACC activation during painful rectal distension in IBS to confer clinical benefits. Secondary aims were to identify other brain regions altered by amitriptyline, and to determine if reductions in cerebral activation are greater during mental stress. METHODS: Nineteen women with painful IBS were randomised to amitriptyline 50 mg or placebo for one month and then crossed over to the alternate treatment after washout. Cerebral activation during rectal distension was compared between placebo and amitriptyline groups by fMRI. Distensions were performed alternately during auditory stress and relaxing music. RESULTS: Rectal pain induced significant activation of the perigenual ACC, right insula, and right prefrontal cortex. Amitriptyline was associated with reduced pain related cerebral activations in the perigenual ACC and the left posterior parietal cortex, but only during stress. CONCLUSIONS: The tricyclic antidepressant amitriptyline reduces brain activation during pain in the perigenual (limbic) anterior cingulated cortex and parietal association cortex. These reductions are only seen during stress. Amitriptyline is likely to work in the central nervous system rather than peripherally to blunt pain and other symptoms exacerbated by stress in IBS.

Adult↗
PubMed1996

A non-selective (amitriptyline), but not a selective (citalopram), serotonin reuptake inhibitor is effective in the prophylactic treatment of chronic tension-type headache.

OBJECTIVES: Although the tricyclic antidepressant amitriptyline is extensively used in the prophylactic treatment of chronic tension-type headache, only few studies have investigated the efficacy of this treatment and the results are contradictory. In addition, the new selective serotonin reuptake inhibiting antidepressants, which are widely used in depression and of potential value in pain management, have never been investigated in a placebo controlled study of tension-type headache. The aim was to evaluate the efficacy of amitriptyline and of the selective serotonin reuptake inhibitor citalopram in chronic tension-type headache. METHODS: Forty non-depressed patients with chronic tension type headache were included in a 32 week, double blind, placebo controlled, three-way crossover study. RESULTS: Thirty four patients completed the trial. Amitriptyline reduced area under the headache curve by 30% compared with placebo (P = 0.002), whereas citalopram had no significant effect (P = 0.68). Explanatory analyses showed that amitriptyline significantly reduced the duration of headache (P = 0.01), headache frequency (P = 0.01), and intake of analgesics (P = 0.02) but not headache intensity (P = 0.12). CONCLUSION: Although amitriptyline did not eliminate the headache, it provided a clinically important reduction of headache in the majority of otherwise treatment resistant patients. The differential effect of amitriptyline and citalopram indicates that mechanisms other than inhibition of serotonin reuptake are involved in the analgesic effect of the tricyclic antidepressants. Amitriptyline, but not citalopram, is valuable in the prophylactic treatment of chronic tension type headache.

Adolescent↗
PubMed2001

Relative contribution of CYP3A to amitriptyline clearance in humans: in vitro and in vivo studies.

The relative contribution of cytochrome P450 3A (CYP3A) to the oral clearance of amitriptyline in humans has been assessed using a combination of in vitro approaches together with a clinical pharmacokinetic interaction study using the CYP3A-selective inhibitor ketoconazole. Lymphoblast-expressed CYPs were used to study amitriptyline N-demethylation and E-10 hydroxylation in vitro. The relative activity factor (RAF) approach was used to predict the relative contribution of each CYP isoform to the net hepatic intrinsic clearance (sum of N-demethylation and E-10 hydroxylation). Assuming no extrahepatic metabolism, the model-predicted contribution of CYP3A to net intrinsic clearance should equal the fractional decrement in apparent oral clearance of amitriptyline upon complete inhibition of the enzyme. This hypothesis was tested in a clinical study of amitriptyline (50 mg, p.o.) with ketoconazole (three 200 mg doses spaced 12 hours apart) in 8 healthy volunteers. The RAF approach predicted CYP2C19 to be the dominant contributor (34%), with a mean 21% contribution of CYP3A (range: 8%-42% in a panel of 12 human livers). The mean apparent oral clearance of amitriptyline in 8 human volunteers was decreased from 2791 ml/min in the control condition to 2069 ml/min with ketoconazole. The average 21% decrement (range: 2%-40%) was identical to the mean value predicted in vitro using the RAF approach. The central nervous system (CNS) sedative effects of amitriptyline were slightly greater when ketoconazole was coadministered, but the differences were not statistically significant. In conclusion, CYP3A plays a relatively minor role in amitriptyline clearance in vivo, which is consistent with in vitro predictions using the RAF approach.

Adult↗
PubMed1999

Amisulpride in medium-term treatment of dysthymia: a six-month, double-blind safety study versus amitriptyline. AMILONG investigators.

Two hundred and fifty patients participated in a 6-month, double-blind study to evaluate safety and efficacy of a medium-term treatment with amisulpride 50 mg/day versus amitriptyline 25-75 mg/day in dysthymia. Patients in treatment groups (165 amisulpride; 85 amitriptyline) were well balanced for demographic and baseline characteristics. A total of 139 patients (93 amisulpride, 46 amitriptyline) completed the study with no statistically significant differences in reasons for premature termination between the two groups. A tendency towards a higher incidence of treatment-emergent adverse events with amitriptyline was observed (73% versus 64% amisulpride). In the amitriptyline group, a statistically significantly higher incidence of central nervous system (41% versus 24%, p=0.004) and autonomic nervous system disorders (45% versus 16%, p < 0.0001) was reported. Conversely, endocrine disorders were more frequent with amisulpride (18% versus 7%, p=0.023). Efficacy was a secondary end-point. Results of the symptom rating scales indicate that both drugs were equally effective: 60% and 62% of patients under amisulpride and amitriptyline, respectively, achieved a reduction > or = 50% of the Montgomery and Asberg Rating Scale total score at end-point. On the item 'global improvement' of the Clinical Global Impression, 67% of amisulpride and 68% of amitriptyline patients were rated as 'very much' or 'much' improved. Results of the present study in a large patient population further confirm the safe use of amisulpride in dysthymia and support its administration upon a medium-term treatment period.

Adult↗
PubMed2003

The relative toxicity of amitriptyline, bupivacaine, and levobupivacaine administered as rapid infusions in rats.

UNLABELLED: Intravascular injection of local anesthetics carries the risk of cardiovascular (CV) and central nervous system (CNS) toxicity. Amitriptyline, a tricyclic antidepressant, has local anesthetic potency that is more than that of bupivacaine. In this study, we compared the CV and CNS toxicity of the local anesthetics bupivacaine and levobupivacaine with that of amitriptyline. Twenty-nine Sprague-Dawley rats had their right external jugular vein and carotid artery cannulated under general anesthesia. On Day 2, rats were sedated with midazolam (0.375 mg/kg intraperitoneally) and received rapid infusions of either 1) bupivacaine, levobupivacaine, or amitriptyline at 2 mg x kg(-1) x min(-1) (5 mg/mL concentration) or 2) normal saline (400 micro L x kg(-1) x min(-1)) through an external jugular vein cannula. Electrocardiogram and arterial blood pressure were measured until the dose to cause impending death was reached (heart rate 50 bpm/asystole or apnea for >30 s). The mean dose required to cause apnea and impending death was significantly larger for amitriptyline (74.0 +/- 21 mg/kg and 74.5 +/- 21 mg/kg, respectively) than for levobupivacaine (32.2 +/- 20 mg/kg and 33.9 +/- 22 mg/kg, respectively) or bupivacaine (21.5 +/- 7 mg/kg and 22.7 +/- 7 mg/kg, respectively) (P < 0.05). A significantly larger dose of amitriptyline, given by rapid infusion, is required to cause CV and CNS toxicity in rats, when compared with bupivacaine and levobupivacaine. IMPLICATIONS: Amitriptyline, a tricyclic antidepressant, has local anesthetic properties and is more potent than bupivacaine. Significantly larger doses of amitriptyline, given by rapid infusion, are required to cause cardiovascular and central nervous system toxicity in rats, when compared with bupivacaine and levobupivacaine.

Amitriptyline↗
PubMed2003

Peripheral antihyperalgesic and analgesic actions of ketamine and amitriptyline in a model of mild thermal injury in the rat.

UNLABELLED: In this study, we examined antihyperalgesic and analgesic actions after local peripheral administration of ketamine and amitriptyline in a rat model of mild thermal injury. Exposure of the hindpaw to 52 degrees C for 45 s under anesthesia produced a subsequent thermal hyperalgesia lasting at least 2 h. The local peripheral administration of ketamine (100-1000 nmol) 15 min before the thermal injury produced an antihyperalgesic effect when injected into the ipsilateral paw, whereas amitriptyline produced both antihyperalgesic (300 nmol) and analgesic (1000 nmol) effects. Administered after the thermal injury, ketamine had no effect, whereas amitriptyline retained its analgesic but not its antihyperalgesic effect. Amitriptyline (300 and 1000 nmol) produced an analgesic action when administered into the normal nonsensitized hindpaw. Both drugs increase paw volume, particularly at larger doses; biogenic amines are not involved in the action of amitriptyline, as was shown previously for ketamine. These results indicate that (a) ketamine produces antihyperalgesia, but not analgesia, when administered locally with a mild thermal injury model; (b) amitriptyline produces both antihyperalgesia and analgesia when administered locally; and (c) the increase in paw volume produced by these drugs occurs by different mechanisms. IMPLICATIONS: This study examines the pain-relieving properties of the local peripheral administration of ketamine and amitriptyline, two drugs in current clinical use, in a thermal injury model of hyperalgesia and demonstrates both antihyperalgesic and analgesic properties. These observations provide support for their potential use as local (e.g., topical) analgesics.

Administration, Topical↗
PubMed2004

Influence of the light schedule on the toxicity of amitriptyline in chick embryos.

The cardiac toxicity of amitriptyline and the effect of the light schedule on it were studied in chick embryos. Fertilized eggs of White Leghorns were incubated under dark conditions and investigated, on two occasions, in the light phase and in the dark phase. Amitriptyline was injected into the air sac of fertilized eggs on the 16th day of incubation. Electrocardiograms were recorded 0 to 60 min after the injection. After the administration of amitriptyline 1 mg/egg in the light phase, the heart rate did not differ compared with that in controls. However, the heart rate was significantly decreased by the administration of amitriptyline 2.5 mg/egg and 5 mg/egg in the light phase. The heart rate was significantly decreased by the administration of amitriptyline 1 mg/egg under dark conditions. In addition, arrhythmia was produced by the administration of amitriptyline under dark conditions. These findings indicate that manipulation of the light schedule has a marked influence on the toxicity of amitriptyline in chick embryos.

Amitriptyline↗
PubMed1987

Cardiovascular effects of paroxetine, a newly developed antidepressant, in anesthetized dogs in comparison with those of imipramine, amitriptyline and clomipramine.

The cardiovascular effects of various antidepressant drugs including paroxetine, imipramine, amitriptyline and clomipramine, administered intravenously, have been assessed. Paroxetine, imipramine, amitriptyline or clomipramine potentiated the response to norepinephrine (0.1 microgram/kg, i.v.) on systemic blood pressure, while paroxetine, imipramine and amitriptyline weakened the response to tyramine (30 micrograms/kg, i.v.). A marked decrease in systemic blood pressure was observed after large doses of each drug (3 and 10 mg/kg of paroxetine; 1-10 mg/kg of imipramine, amitriptyline or clomipramine); and half of the animals died following administration of 10 mg/kg of imipramine, amitriptyline or clomipramine. Paroxetine did not show a marked effect on heart rate at a dose of up to 3 mg/kg, although 0.1-3 mg/kg of imipramine, amitriptyline or clomipramine dose-dependently caused tachycardia. ECG disturbances were observed in animals administered 10 mg/kg of imipramine, amitriptyline or clomipramine; but in contrast, 10 mg/kg of paroxetine caused only slight changes in the ECG. Prolongation of atrio-ventricular conduction time was observed with all the drugs. It was concluded that the effects of paroxetine on the canine heart are more mild in comparison with other tricyclic antidepressants used, although its pharmacological features are essentially similar to those of other drugs.

Amitriptyline↗