Psychopharmacology (Berl). 2004 Jan;171(3):270-6. Epub 2003 Sep 04.
Gender difference in the prevention of hyperanxiety in adult prenatally stressed rats by chronic treatment with amitriptyline.

Poltyrev T, Weinstock M.

Department of Pharmacology, School of Pharmacy, Hebrew University Medical Centre, Ein Kerem, 91120, Jerusalem, Israel.

OBJECTIVE. The study determined whether oral administration of amitriptyline for 6 weeks from before puberty to prenatally stressed (PS) male and female rats could prevent hyperanxiety in adulthood. METHODS. Sprague-Dawley (12) rat dams were stressed by restraint in cylinders thrice daily for 45 min during the last week of pregnancy. Their offspring and those from unstressed dams (12) were given amitriptyline (4.5 mg/kg per day) in the drinking water between 4 and 10 weeks of age. Behaviour was assessed in the elevated plus maze (EPM) in week 10 in group 1 while still receiving the drug; in group 2, 2 weeks after stopping the drug, and in group 3, as in group 2, but after prior exposure to an open field (OF). RESULTS. When tested while receiving the drug, no clear anxiolytic effect was seen in PS rats, and anxiety was actually increased in control rats, as indicated by the greater amount of time in closed arms of the EPM. Significant anxiolytic effects of amitriptyline (increase in time in open arms of EPM) were seen 2 weeks after stopping the drug in PS females. It could only be demonstrated in PS males after their anxiety in the EPM had been increased as a result of prior exposure to the open field. CONCLUSIONS. Chronic early treatment with amitriptyline can prevent the development of hyperanxiety in PS rats in adulthood. This effect is only detectable after cessation of drug treatment. The anxiolytic effect is more readily detected in females.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12955287&dopt=Abstract Elavil amitriptyline[PubMed - in process]




Kidney Int. 2003 Oct;64(4):1356-64.
Amitriptyline eliminates calculi through urinary tract smooth muscle relaxation.

Achar E, Achar RA, Paiva TB, Campos AH, Schor N.

Nephrology Division, Escola Paulista de Medicina/Universidade Federal de Sao Paulo, Brazil.

BACKGROUND: We investigated the effects of amitriptyline in the urinary tract smooth muscle and urolithiasis. METHODS: Cats presenting with obstructive acute renal failure (ARF) received amitriptyline, and renal function and survival rates were analyzed. Isometric contractions and membrane potentials of rat, pig, or human isolated urinary tract smooth muscle were recorded in the presence or absence of amitriptyline. RESULTS: Twenty cats with obstructive ARF caused by urethral plugs received amitriptyline. In all cases, plugs were completely eliminated, and renal function returned to normal, with a 100% survival rate in the follow-up. Amitriptyline produced potent relaxations in rat urethral strips, accompanied by significant reductions in urethral ring membrane potential. This effect was prevented by pretreatment of urethral rings with 4-aminopyridine (4-AP), a voltage-dependent potassium channel blocker. Amitriptyline abolished in a reversible manner acetylcholine-, bradykinin-, and KCl-induced contractions in rat isolated bladder, and this effect was also prevented by 4-AP. Of interest, spontaneous and KCl-induced contractions of pig and human isolated ureter were also blocked by amitriptyline. CONCLUSION: Our results indicate that amitriptyline is an effective and potent relaxant of urinary tract smooth muscle and this effect is mediated by opening of voltage dependent-potassium channels. We suggest that amitriptyline administration may help to promote elimination of urinary calculi.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12969154&dopt=Abstract Elavil amitriptyline[PubMed - in process]




J Nerv Ment Dis. 1975 Jan;160(1):34-41.
Relative safety of amitriptyline in maintenance treatment of depression.

DiMascio A, Klerman GL, Prusoff B.

In the course of long term treatment with amitriptyline of 212 depressed women, the patients' somatic complaints were assessed. These somatic complaints included most symptoms generally attributed as being adverse effects of amitriptyline and other tricyclics. The reputed adverse effects were very often reported by patients prior to the initiation of antidepressant medication. Except for reports of dryness of mouth, all somatic complaints were reduced in frequency and intensity during the course of clinical improvement. When patients relapsed, regardless of whether they were or were not on maintenance medication, these somatic complaints returned. Except for dryness of mouth, no relationship between somatic complaints and dosage of amitriptyline was found. Amitriptyline is relatively safe. No espisodes of death, cardiac arrhythmia liver, blood or central nervous system reaction occurred.

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Scand J Clin Lab Invest. 1976 Jan;36(1):7-15.
Cardiac effects of amitriptyline in rats.

Thorstrand C, Bergstrom J, Castenfors J.

The effect of intravenous amitriptyline (0.5-2 mg/kg) on heart rate, blood pressure, ECG, and electrolytes in plasma and heart muscle was studied in rats. In addition, the effect on monophasic action potentials was studied in rats with open chest. Amitriptyline caused a significant decrease in blood pressure and heart rate and a significant prolongation of QRS and PQ duration. At the time of maximal QRS prolongation (mean +94%) the duration of monophasic action potentials was virtually unchanged. Beta-adrenergic blockade by means of pretreatment with 0.1 mg propranolol did not influence the amitriptyline-induced prolongation of QRS duration. Amitriptyline administration causing obvious QRS prolongation induced no detectable changes in plasma and heart muscle electrolytes. The results contradict adrenergic dominance or marked imbalance between intra- and extra-cellular electrolytes as a cause of the ECG changes. The present data indicate that the amitriptyline effect is compatible with a direct quinidine-like action on the heart, resulting mainly in a slowing of impulse propagation in the intracardiac conduction system.

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Eur J Pharmacol. 1992 May 12;226(1):43-52.
Effects of chronic anethole trithione and amitriptyline treatment on rat parotid gland signalling.

Glenert U.

Department of Pathology and Medicine, Royal Dental College, Panum Institute, Copenhagen, Denmark.

The present study examines the mechanism(s) of action of anethole trithione (Sulfarlem S25) compared to the sialogogue pilocarpine. The chronic effects (7 days of treatment) of anethole trithione, pilocarpine and/or amitriptyline on autonomic receptor binding (homogenates) were measured together with parallel tests of stimulation-induced rises in delta [Ca2+]i in collagenase-isolated rat parotid acini. The results revealed that chronic treatment with amitriptyline resulted in significantly increased rises in delta [Ca2+]i after stimulation with 20 microM of carbachol or adrenaline, and a significant increase in muscarinic acetylcholine receptor density. In addition, anethole trithione also increased cholinergic and adrenergic responsiveness. The double treatment of amitriptyline and anethole trithione or amitriptyline and pilocarpine did, however, prevent the rise in delta [Ca2+]i observed under conditions when these drugs were administered alone. Furthermore, anethole trithione, but not pilocarpine, was able to prevent the amitriptyline-induced upregulation in muscarinic acetylcholine receptor density. In conclusion, the experimental data presented in this study are compatible with the hypothesis that anethole trithione might stimulate some post-receptor effect in the coupling to the secretory response. In addition, this study supports the beneficial effects of anethole trithione in treating drug-induced xerostomia.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1327842&dopt=Abstract Elavil amitriptyline




Hum Exp Toxicol. 1992 Sep;11(5):363-7.
Determination of amitriptyline in the hair of psychiatric patients.

Tracqui A, Kreissig P, Kintz P, Pouliquen A, Mangin P.

Institut de Medecine Legale, Strasbourg, France.

A study was conducted on 60 psychiatric patients to evaluate the reliability of a drug-exposure screening test based on gas chromatography/mass spectrometry analysis of hair samples for amitriptyline, and the possibility of using the hair concentrations of amitriptyline to monitor patients' therapeutic compliance. The qualitative test was found to be very reliable (sensitivity 93.3%; specificity 100%; positive and negative predictive values 100 and 93.8%) in assessing the consumer status of patients over a period of 2 months before analysis. Hair levels of amitriptyline ranged from 0 to 17.21 ng mg-1. A significant relationship (r = 0.563; P < 0.002) was found between the hair concentrations and the cumulative intake of amitriptyline over the studied period, but was not judged close enough to estimate one individual's therapeutic compliance. The results are discussed in the light of existing literature.

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Clin Auton Res. 1992 Feb;2(1):5-15.
Effects of chronic amitriptyline administration on saliva from the parotid and submandibular glands of the rat.

Yu JH.

Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, DC.

The effect of prolonged treatment with amitriptyline on the secretory activity of rat salivary glands evoked by parasympathetic nerve stimulation and isoprenaline administration has been studied. Low doses of amitriptyline (10 mg/kg per day for 2 or 4 weeks), did not significantly affect salivary flow evoked by either parasympathetic nerve or isoprenaline stimulation. Higher doses of amitriptyline (50 mg/kg/day for 2 or 4 weeks) however, markedly decreased parasympathetic-evoked salivary secretion (flow and volume) from both parotid and submandibular glands, while isoprenaline-evoked secretions were unaffected. Sodium, potassium, and calcium concentrations of nerve-elicited or isoprenaline-evoked saliva were not significantly altered by amitriptyline treatment. Protein concentration and amylase activity of nerve-elicited parotid saliva were, however, greatly increased by chronic amitriptyline administration. Possible mechanisms for drug-induced increase in nerve-elicited salivary protein concentration include changes in cholinergic receptor binding, release of neuropeptides and variations in phosphatidylinositol turnover, which need further study.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1379093&dopt=Abstract Elavil amitriptyline