Drugs online research references
Acta Pharmacol Toxicol (Copenh). 1980 Mar;46(3):161-70.
Electrocardiographic and cardiovascular changes in cats and dogs caused by high doses of amitriptyline given as conventional tablets or a sustained release preparation.
Boeck V, Jorgensen A.
Electrocardiographic and haemodynamic changes have been compared in anesthetized cats and in conscious dogs after high doses of amitriptyline given as conventional tablets or as a sustained release form. Plasma or serum levels of amitriptyline and nortriptyline were determined. In anaesthetized cats tablets caused marked ECG changes in all 6 animals combined with pronounced acidosis in 3 of the animals. The sustained release form caused no electrocardiographic changes in 4 animals and moderate disturbances in 2 animals, without acidosis in any of the 6 cats. Almost identical haemodynamic changes were seen in both groups. The plasma levels did not indicate poorer absorption from one preparation than from the other. In conscious dogs tablets caused marked clinical signs including restlessness, sedation and convulsions (2 dogs). Pronounced electrocardiographic changes were seen in all 4 dogs. Bundle branch block developed in 3 dogs. The sustained release preparation caused slight to moderate sedation and no convulsions. Pronounced electrocardiographic changes without bundle branch block were seen in one dog. Moderate changes were seen in the remaining dogs. Acidosis was most pronounced after the tablets. The serum drug levels clearly show that the absorption is much slower after administration of the sustained release preparation than after tablet administration and that somewhat lower amounts of drug are absorbed from the sustained release preparation than from tablets. It is evident from the present studies, that administration of high doses of amitryptyline as a sustained release preparation causes less toxic manifestations than given as conventional tablets. Part of the explanation may be that less amitryptyline is absorbed from the sustained release preparation than from tablets because of the high dose (dogs), but the main reason is most likely that the absorption from the sustained release preparation is much slower than the absorption from tablets.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7361572&dopt=Abstract
Br J Pharmacol. 1977 May;60(1):21-7.
Plasma nortriptyline and cardiac responses in young and old rats.
Bonaccorsi A, Franco R, Garattini S, Morselli PL, Pita E.
1. The relationship between plasma concentrations and cardiac effects of nortriptyline was studied in anaesthetized young and old rats. 2. Nortriptyline was administered by two consecutive intravenous infusions which resulted in a peak plasma concentration followed by steady state values. Increasing infusion rates were followed by proportional increases in the drug plasma concentrations ranging from 0.15 to 6.0 microgram/ml. 3. In young rats, nortriptyline induced an increase in the heart rate, a right rotation of the electrical axis and a prolongation of the PQ interval. Heart rate changes were not correlated with nortriptyline plasma concentrations, while significant correlations were found for the other two parameters. Plasma concentrations inducing 20% increase of the PQ interval and 40 degrees rotation of the electrical axis were 1.65 microgram/ml respectively. Arrhythmias occurred at concentrations higher than 5.2 microgram/ml. 4. Nortriptyline caused more severe cardiac effects in old than in young animals. However, plasma concentrations of nortriptyline in old rats were two to five times higher than those found in young rats at similar infusion rates. A higher concentration of the drug at its sites of action seems to be responsible for the more severe cardiac toxicity of nortriptyline observed in old rats.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=884387&dopt=Abstract
Neuropsychopharmacology. 1990 Feb;3(1):51-9.
Serotonergic and catecholaminergic reuptake inhibitors have opposite effects on the ultrasonic isolation calls of rat pups.
Winslow JT, Insel TR.
Laboratory of Clinical Science, National Institute of Mental Health, NIHAC, Poolesville, MD 20837.
Rat pups emit a highly stereotyped and well-characterized distress call in the ultrasonic range when socially isolated. We compared the modulatory influence of catecholamines and indoleamines on rat pup ultrasonic calls using pharmacologic probes. Administration of low doses of monoamine reuptake inhibitors produced significant, selective changes in the calls emitted by isolated 10-day-old pups. Acute administration of clomipramine (CMI; relatively 5-HT specific) reduced the rate of calling at low doses (1.0 and 5.0 mg/kg [3.2 and 18.0 mmol/kg] SC) but had reduced efficacy at higher doses (10 and 20 mg/kg [32.0 and 63.7 mmol/kg] SC). Motor activity and rectal body temperature were unaffected at these doses. Similarly, low doses of other 5-HT-selective uptake inhibitors, such as paroxetine (1.0 mg/kg [3.1 mmol/kg] SC) and citalopram (1.0 mg/kg [3.09 mmol/kg] SC), virtually eliminated isolation calling. The effects of CMI were not antagonized by either naltrexone (0.1 mg/kg [0.28 mmol/kg] SC) or Ro 15-1788 (5.0 mg/kg [16.5 mmol/kg] SC). Desipramine (DMI; norepinephrine [NE] specific) significantly increased calling rates at all doses tested (1.0 to 10.0 mg/kg [3.8 to 75 mmol/kg] SC). These effects were associated with significant reductions in body temperature, but not motor activity. Similar increases in the rate of isolation calling, reduction in rectal body temperature, and an increase in motor activity were produced by low doses of mazindol (0.5 mg/kg [1.75 mmol/kg] SC) and nortriptyline (1.0 mg/kg [19 mmol/kg] SC). In an additional study, the chronic effects of CMI and desipramine were evaluated with treatment beginning within 24 hours after birth.(ABSTRACT TRUNCATED AT 250 WORDS)
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2137699&dopt=Abstract
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