ABSTRACT
The IV infusion of nortriptyline and amitriptyline (0.5 mg/kg/min) in anesthetized cats produced death within 60 min of continuous infusion. The tricyclic antidepressant agents produced a quinidine-like depression of the myocardium characterized by bradycardia, depression of contractile force, conduction defects, bradyarrhythmias, and hypotension. The simultaneous IV infusion of isoproterenol (0.1 microgram/ kg/min) produced significant protection against death produced by the TCA drugs. The results suggested that the positive chronotropic, inotropic, and dromotropic actions of isoproterenol may all be contributory factors in the protection. Pretreatment with a large dose of physostigmine (0.2 mg/kg) produced a rightward shift of the nortriptyline time-mortality curve. The small degree of protection produced by the anticholinesterase drug may be due to a respiratory stimulant action rather than a cardiac action.
Subject(s)
Amitriptyline/toxicity , Isoproterenol/pharmacology , Nortriptyline/toxicity , Physostigmine/pharmacology , Animals , Blood Pressure/drug effects , Cats , Drug Interactions , Electrocardiography , Female , Heart Rate/drug effects , Infusions, Parenteral , Male , Myocardial Contraction/drug effectsSubject(s)
Amitriptyline/toxicity , Ouabain/pharmacology , Sympathomimetics/pharmacology , Amitriptyline/antagonists & inhibitors , Animals , Arrhythmias, Cardiac/chemically induced , Blood Pressure/drug effects , Cats , Dobutamine/pharmacology , Dopamine/pharmacology , Electrocardiography , Heart Rate/drug effectsSubject(s)
Adrenergic alpha-Agonists/pharmacology , Adrenergic beta-Agonists/pharmacology , Blood Glucose/metabolism , Liver Glycogen/metabolism , Animals , Cats , Cyclic AMP/metabolism , Female , Isoproterenol/pharmacology , Liver/drug effects , Male , Phenylephrine/pharmacology , Phosphorylase a/metabolism , Time FactorsABSTRACT
A narcissus alkaloid, pretazettine hydrochloride (PTZ) has been shown to be active against spontaneous AKR leukemia. The long-term treatment with PTZ begining at 5--7 months of age of a group of AKR mice containing 10--20% of advanced leukemic mice significantly prolonged the life span of the group. The therapeutic effectiveness of PTZ has been compared with several standard antileukemic drugs. PTZ decreased the AKR virus titer in the circulating blood of mice and its antiviral activity in AKR virus infected NIH/3T3 cells has been confirmed by XC assay.
Subject(s)
Alkaloids/therapeutic use , Leukemia, Experimental/drug therapy , AKR murine leukemia virus/isolation & purification , Animals , Cells, Cultured , Drug Evaluation, Preclinical , Female , Leukemia Virus, Murine/analysis , Leukemia, Experimental/microbiology , Leukemia, Experimental/mortality , Mice , Mice, Inbred AKR , Plants, MedicinalABSTRACT
We had previously reported that drugs which stimulate beta-2 adrenergic receptors decreased the hyperkalemia produced by infused KCI and thus protected animals against KCI intoxication; these effects were mediated by an action of beta-2 agonists which enhanced tissue uptake of K+. In this study, cats were given an i.v. infusion of KCI which was not lethal in control animals. Acute adrenalectomy markedly increased the hyperkalemic and mortality responses to infused KCI. This impairment in K+ metabolism was corrected by the administration of epinephrine but not by hydrocortisone. Pretreatment with propranolol (which blocks beta-1 and beta-2 receptors) and H35/25 (which blocks beta-2 receptors) produced a similar impairment in K+ metabolism; on the other hand, practolol (which blocks beta-1 receptors) had little or no effect on the mortality and hyperkalemic responses to infused KCI. Evidence that KCI stimulates an adrenal release of catecholamines is presented. This stimulation of adrenal release may be important in conferring resistance to intoxication produced by infused KCI since the released amines can attenuate the KCI-induced hyperkalemia via a beta-2 action which enhances tissue uptake of K+.