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At least 1,243 records · Page 69Linked to original sources
PubMed1992

Blood pressure effects of tranylcypromine when prescribed singly and in combination with amitriptyline.

Data on blood pressure was extracted from the findings of a 6-week double-blind study that was carried out to evaluate the efficacy and safety of prescribing tranylcypromine (TCP) singly and in combination with amitriptyline (AMI). The effect of TCP on blood pressure was one of the methods used to evaluate its safety. Target daily doses of medication for the final 2 weeks of the study were: TCP 30 mg, AMI 150 mg, or the two in combination. Because of side effects, mean daily doses actually achieved were lower: single TCP 18.5 mg; single AMI 114.3 mg; combined TCP/AMI: TCP 19.7 mg, AMI 108.7 mg. When TCP alone was prescribed, a significant fall in diastolic blood pressure in the standing position was noted and orthostatic hypotension was more frequently observed. Dizziness was complained of on at least one occasion in over three quarters of patients on TCP/AMI. No correlation between blood pressure effects and dizziness was detected and there were no other troublesome side effects from this antidepressant combination. The study concluded that although TCP's overall effect on mean blood pressure readings when prescribed alone or in combination was small, its orthostatic effect is noteworthy and should be borne in mind by the prescribing clinician.

Adult↗
PubMed1992

[Analysis of 20 cases of amitriptyline poisoning].

20 cases of amitriptyline poisoning have been reported. The main symptoms were come in different degrees, pupil dilatation, tachycardia, retention of urine. Raising of blood pressure and subnormality of body temperature appeared in part of patients. There were convulsive attacks in some severe patients. EKG were abnormal in half of patients. Besides gastric lavage and acceleration of excretion, using of physostigmine was one of the important reused steps, it often was the determinate factor to get success. Convulsive attack was the main dangerous to death. Some discussions have been made about relative problems.

Adult↗
PubMed1992

Nonsteroidal management of canine pruritus with amitriptyline.

Thirty-one dogs with nonlesional pruritus were treated with amitriptyline (1 mg/kg orally q12h) to determine its efficacy in the management of canine allergic pruritus. Seventeen dogs were known to be atopic, 8 were presumed to be atopic, and 6 had pruritus of undetermined etiology. Pruritus was virtually eliminated in 5 (16.1%) dogs, reduced by approximately 50% in another 5 (16.1%) dogs, and not changed in the remaining 21 dogs. Side effects were uncommon.

Amitriptyline↗
PubMed1991

[Levels of amitriptyline and its metabolites in the treatment of depression].

The authors assessed in a 21-day investigation the levels of amitriptyline and its metabolites in plasma and saliva, using the RIA method, in an attempt to reveal the relationship between the therapeutic effect and the assessed concentrations. They did not find a clear relationship between the therapeutic effect and plasma levels; when eliminating extreme maximal and minimal values, we may speak of concentrations where clinical improvement is recorded: from 150 to 450 micrograms/l. The concentration in saliva correlated at higher levels with the plasma concentration; this gives a theoretical chance of screening by this method. From the clinical aspect it is essential to express an opinion on the development of side-effects in relation to plasma levels. This problem will be discussed in a subsequent paper.

Adult↗
PubMed1990

The influence of ethanol on the distribution of amitriptyline and nortriptyline in rats.

The influence of ethanol in single and multiple doses on concentration-time profile of amitriptyline (1) and nortriptyline (2) in rat serum, brain, heart, and liver was studied. AUC0-6 values were calculated and statistically compared as well as cmax values in serum and tissues. Ethanol inhibited N-demethylation of 1 and therefore 2 has not been detected in biological material. AUC0-6 and cmax values were less than in control group. All AUC0-6 and cmax values for 1 in ethanol treated groups of rats were statistically significant compared with the control group.

Amitriptyline↗
PubMed1990

[Inhibited effects of amitriptyline on rabbit basilar and mesenteric artery rings].

The effects of amitriptyline (Ami) on isolated rabbit basilar and mesenteric artery rings were studied and compared with verapamil (Ver). Ami inhibited the contraction of the rabbit basilar and mesenteric artery rings evoked by KCl, CaCl2 and norepinephrine, noncompetitively. The pD'2 values for Ami to antagonize effects of KCl, CaCl2, NE on both arteries were 5.79 +/- 0.10 and 4.97 +/- 0.12 (P less than 0.01), 4.50 +/- 0.30 and 4.58 +/- 0.12 (P greater than 0.05), 5.80 +/- 0.13 and 5.56 +/- 0.12 (P less than 0.01), respectively. The characteristics of such effects of Ami were the same as Ver. The results suggest that Ami may block calcium channels and inhibit rabbit basilar artery selectively.

Amitriptyline↗
PubMedDate not supplied

Repeated treatment with imipramine, amitriptyline or electroconvulsive shock does not affect the 8-OH-DPAT-induced increase in food intake in free feeding rats.

We studied the effect of repeated treatment with imipramine, amitriptyline (10 mg/kg po, twice daily for 14 days) or electroconvulsive shock (ECS, once daily for 10 days) on the 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT)-induced increase in food intake in free feeding rats. The response to 8-OH-DPAT, measured 24 h after the last administration of the antidepressant drugs or ECS, was not modified. These results, together with literature data, indicate that the presynaptic 5-HT1A receptors involved in the 8-OH-DPAT-induced feeding are not affected by long-term antidepressant administration.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMedDate not supplied

[The isolation of amitriptyline from cadaveric material using acetonitrile].

Method of amitriptyline isolation from the cadaveric material using acetonitrile as extractant is suggested. This method makes it possible to extract in average 76.09% of substance previously added in quantity of 1 mg to 25 g of the liver. Method was successfully used in analysis of expert material.

Acetonitriles↗
PubMed1989

Recurrent gastroesophageal symptoms and precordial pain in a gastrectomized man improved by amitriptyline. Physiologic, metabolic, endocrine, neurochemical and psychiatric findings.

A 57-year-old white man presenting frequent recurrent chest and precordial pain, heartburn (pyrosis) and post-prandial vomiting for the previous 33 years (one to two years after Bilroth II gastrectomy) was submitted to cardiovascular, endoscopic, radiologic and biochemical studies with negative results. Doctors recommended surgical operation because of an excessively long afferent loop, Several biologic markers were performed at our hospital (intestinal pharmacomanometry, i.m. clonidine test, plasma neurotransmitters plus hormones, oral glucose tolerance test, plasma insulin, etc.), revealing an autonomic nervous system (ANS) imbalance characterized by hyperactivity of the cholinergic plus hypoactivity of the noradrenergic central system. Psychiatric evaluation demonstrated Dysthymic Depression. Treatment with a small daily dose of amitriptyline (a drug which enhances central noradrenergic activity and exerts powerful anticholinergic effects) suppressed symptoms, normalized physiological plus hormonal plus neurochemical parameters and made depressive manifestations disappear. The results suggest that the ANS imbalance was related to depressive syndrome and potentiated by neurohumoral disorders depending on duodenal and jejunal exclusion, and on intestinal post-prandial hyper-osmolarity.

Amitriptyline↗
PubMed1989

[Determination of amitriptyline hydrochloride by zero-current oscillo-potentiometric and bipotentiometric methods].

Using platinum plate coated with PVC membrane as indicator electrode, amitriptyline hydrochloride was titrated with sodium tetraphenylborate by zero-current oscillo-potentiometry titration and zero-current oscillo-bipotentiometric titration. Both methods are precise, audio-visual, simple and convenient and can be used in the determination of other medicines.

Amitriptyline↗
PubMedDate not supplied

Comparative effects of the antidepressants amitriptyline, mianserin and adinazolam on hemodynamics and ECG in myocardial infarcted dogs.

This study was undertaken to examine the effects of mianserin (MIA), a tetracyclic antidepressant, and adinazolam (ADI), a new benzodiazepine antidepressant on cardiac function and electrocardiogram in normal and infarcted hearts of anesthetized dogs, and to compare the effects with those of amitriptyline, a commonly used tricyclic antidepressant. The parameters measured were: heart rate (HR); mean arterial blood pressure (MP); aortic flow (AF); maximal rate of increase of left ventricular pressure (LV dp/dt); blood flow of left circumflex of left coronary artery (CAF) and PQ and QRS intervals. The double product (DP) was calculated from HR and the arterial pressure. AMI increased HR, DP, LV dp/dt and CAF in the normal group, while in the infarcted group, AMI increased HR, DP and CAF, but decreased LV dp/dt at 3 mg/kg. AMI at 2 and 3 mg/kg prolonged QRS intervals in the infarcted groups. MIA increased HR and DP in the normal group at doses of 1 mg/kg or more, while in the infarcted group it produced only slight effects in hemodynamic parameters and PQ and QRS intervals. ADI had little effect on hemodynamics and PQ and QRS intervals in the normal group. However, it decreased LV dp/dt, CAF, MP at 3 mg/kg in the infarcted group. In conclusion, AMI markedly influenced cardiac hemodynamics and QRS interval in the myocardial infarcted group, while, on the other hand, MIA and ADI, in clinical doses, had only a slight effect on hemodynamics and PQ and QRS intervals in the infarcted group. Thus MIA and ADI were safer than AMI in the animals with myocardial infarction.

Amitriptyline↗
PubMedDate not supplied

[Various hemodynamic indicators in patients with endogenous depression before and during amitriptyline treatment].

The hemodynamic tests using radiocardiographic method, as well as the evaluation of mental status with the help of rating scales was made in 34 patients with endogenous depression. Following differences between depressive patients and age-matched controls were found: higher heart rate (HR), higher systolic arterial pressure (SAP), higher diastolic arterial pressure (DAP), slightly higher systolic index (SI), and higher total peripheral resistance index (TPRI). In addition it was found that HR and TPRI show positive correlation with the intensity of anxiety in Hamilton's++' scale. Two-week lasting amitriptyline treatment partially corrects the unfavourable hemodynamic effects.

Adult↗
PubMedDate not supplied

Phenolic metabolites of amitriptyline and nortriptyline in rat bile.

Anesthetized bile fistula rats received amitriptyline (AT), its N-oxide (AT-NO), or nortriptyline (NT) at doses of 72 mumol/kg ip, and bile was collected for 6-9 hr. Isolation of metabolites was achieved by enzymic deconjugation and repeated TLC of extracted aglycones. Purified compounds were characterized by UV, NMR, and mass spectrometry, by color reactions, and by chemical interconversions. Besides the alcohols E-10-hydroxy-AT and 10,11-dihydroxy-AT, the phenol E-2-hydroxy-AT occurred as a major AT metabolite, while 2,10- and 2,11-dihydroxy-AT, 2,10,11-trihydroxy-AT, and 2-hydroxy-3-methoxy (or 3-hydroxy-2-methoxy)-AT were present in smaller quantities. Further minor metabolites were 2-hydroxy-11-oxo-AT, 3-hydroxy-AT, 3,11-dihydroxy-AT, and its dehydration product 3-hydroxy-10,11-dehydro-AT. The exact position of the functional groups was elucidated by the nuclear Overhauser effect (NOE) in NMR spectroscopy and by analyzing metabolite patterns in the bile of rats given E- or Z-10-hydroxy-AT. Administration of AT-NO led to a larger proportion of methylated catechols and a smaller one of 10-hydroxy metabolites. Besides the tertiary amines, rats given AT or AT-NO excreted the demethylated analogues of some of the hydroxylation products. The latter also occurred as metabolites of NT, the ratio of aromatic and aliphatic hydroxylation being lower than with AT or AT-NO. Urine of rabbits treated orally with AT contained mono- and dihydroxylated metabolites resulting from attack at positions 2, 3, 10, and/or 11 and the same methylated catechols as rat bile.

Amitriptyline↗
PubMedDate not supplied

Glucuronides of hydroxylated metabolites of amitriptyline and nortriptyline isolated from rat bile.

Polar conjugates were isolated from the bile of rats given amitriptyline (AT, unlabeled or labeled with 14C), nortriptyline (NT), or 10-hydroxy (10-OH) derivatives of the drugs. The procedure involved extraction on a column of polystyrene resin, elution with methanol, and separation by preparative TLC followed by reversed phase HPLC. Individual metabolites were characterized by NMR spectroscopy and fast atom bombardment mass spectrometry and by enzymatic or acid deconjugation with subsequent identification of aglycones and glucuronic acid. Conversely, they were compared with conjugates obtained from hydroxy compounds by incubation with rat liver microsomes and UDP-glucuronic acid. Glucuronides isolated from the bile of rats given AT were derived from 2-OH-AT, (E)- and (Z)-10-OH-AT, 2-hydroxy-3-methoxy- (or 3-hydroxy-2-methoxy) AT, 10, 11-(OH)2-AT, and some of the N-demethylated analogues of these compounds. In most cases, 10-OH compounds form two diastereoisomeric glucuronides produced from the enantiomeric alcohols; 10, 11-(OH)2 metabolites occur as cis- and trans-isomers that are conjugated with glucuronic acid. Administration of synthetic (E)- and (Z)-10-OH-AT and -NT leads to the excretion of their glucuronides along with conjugates formed after demethylation and/or introduction of a second OH group. NT gives rise to 2-OH-NT glucuronide besides those conjugates derived from (E)-10-OH-NT. No glutathione conjugates could be detected.

Amitriptyline↗
PubMed1986

Pharmacologic evidence that high dose chronic amitriptyline and desipramine down-regulate alpha 2-receptor-mediated hypothermia in the rat.

The effects of a three week course of treatment of amitriptyline (AMI) and desipramine (DMI) (3.2 and 10 mg/kg, s.c., b.i.d.) were studied on the hypothermic response to clonidine (0.1 mg/kg, s.c.) in male adult albino rats. Single doses of clonidine in normal unmedicated rats produced a marked (about 2 degrees C) fall in body temperature. In contrast, 0.9% NaCl control injections had no significant effect. The clonidine-induced hypothermia was prevented by yohimbine pretreatment (3.2 mg/kg, i.p., 1/2 hr before), suggesting an alpha 2-mediated response. On days 8 and 14 of chronic tricyclic antidepressant (TCA) treatment, the hypothermic response was prolonged. Four days after the abrupt withdrawal of 20 days of TCA treatment (10 mg/kg, s.c., b.i.d.), the clonidine-induced hypothermia response was attenuated consistent with down-regulation of alpha 2-receptors. This latter effect was not observed with a dose of 3.2 mg/kg, s.c., b.i.d. of either TCA.

Amitriptyline↗
PubMedDate not supplied

On the role of noradrenergic neurotransmission in the action of desipramine and amitriptyline in animal models of depression.

Three weeks of treatment with desipramine (DMI) and amitriptyline (AMI) reduced the hypothermic action of clonidine in rats. Both electrolytic and 6-hydroxydopamine lesions of the locus coeruleus (LC) and administration of DSP-4 counteracted the reduction of clonidine hypothermia produced by antidepressants. Lesions of the LC and DSP-4 administration also antagonized the anti-immobility action of single doses of DMI but failed to modulate the action of AMI in the forced swim test. Chronic DMI action on the rat immobility was reduced by 6-hydroxydopamine lesions of the LC: other lesions (electrolytic, DSP-4) were ineffective. Electrical stimulation of the LC increased the rat activity in the forced swim paradigm, producing an effect similar to that of antidepressants. The anti-immobility effect of DMI as well as LC stimulation were antagonized by drugs blocking alpha-adrenoceptors (phenoxybenzamine, prazosin) but not by propranolol, a non-selective antagonist of beta-adrenoceptors. On the other hand, the anti-immobility action of AMI was unchanged by all adrenolytics used in that study. The results indicate that the LC system and alpha 1-adrenoceptors play an important role in the antidepressive action of DMI, but not AMI, in the forced swim test.

Amitriptyline↗
PubMed1988

Dexamethasone suppression test status does not predict differential response to nortriptyline versus amitriptyline.

Thirty-five (35) inpatients with nonpsychotic major depression were randomly assigned to either amitriptyline or nortriptyline on a double-blind basis, following a 4- to 10-day placebo run-in period. Thirty-two patients completed at least 3 weeks of active medication. The 1.0-mg dexamethasone suppression test (DST) was performed before treatment. Twelve of 32 patients were DST nonsuppressors. Both medications were equally effective. Pretreatment DST status failed to predict overall response to both medications combined. DST status also did not predict differential medication response. These data argue, along with several other studies, that pretreatment DST status may be of limited value in selecting a particular tricyclic antidepressant compound.

Adult↗