Behavioral and neuropharmacological toxicology of the macrocyclic ether 18-crown-6
| Autor: | W J Conroy, J. A. McKelvey, S. C. Gad, K A Turney |
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| Rok vydání: | 1978 |
| Předmět: |
Agonist
Male medicine.medical_specialty medicine.drug_class Health Toxicology and Mutagenesis Receptors Drug Unsteady gait Ether Mice Inbred Strains Toxicology Serotonergic chemistry.chemical_compound Electrolytes Mice Species Specificity Ethers Cyclic Internal medicine Crown Ethers Male rats medicine Animals Cholinesterases Receptor Pharmacology Chemical Health and Safety Behavior Animal Chemistry Public Health Environmental and Occupational Health Muscle weakness Brain General Medicine Organ Size Rats Endocrinology Anesthesia Reflex Rabbits medicine.symptom Nervous System Diseases |
| Zdroj: | Drug and chemical toxicology. 1(4) |
| ISSN: | 0148-0545 |
| Popis: | 18-CROWN-6 was assessed for neurologic effects in rats, mice, and rabbits by intravenous (IV) and intraperitoneal (IP) routes of administration. Male rats and mice exhibited no effects with IV doses to 20 mg/kg. Given IP doses of 20 to 160 mg/kg/day, rats and mice exhibited numerous signs, including aggression, tremors, muscle weakness and a degradation of some reflexes. All signs faded after four days when dosage levels were kept constant, but returned when the dose was doubled. All signs disappeared upon discontinuance of exposure. Treatment with PCPA (p-chlorophenylalanine) or dibenzyline caused most signs to disappear. Rabbits given 6.0 mg/kg/day IV displayed tremors, hyperactivity, unsteady gait and stereotypic behavior, with acclimation as in rats and mice. 18-CROWN-6 had no activity in isolated tissue preparations unless it was first incubated with tissues. PCPA and dibenzyline reversibly blocked the actions of incubated 18-CROWN-6 on isolated tissue. 18-CROWN-6 is hypothesized to be metabolized to a serotonergic agonist. |
| Databáze: | OpenAIRE |
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