Subject(s)
Acetylcholine/pharmacology , Medulla Oblongata/drug effects , Neurons/drug effects , Norepinephrine/pharmacology , Animals , Cats , Female , Iontophoresis , MaleABSTRACT
Clonidine (5, 15, 50 micrograms/Kg i.v) caused dose dependent initial transient pressor response which was blocked by cadmium acetate (1 mg/Kg i.v) in dose dependent manner in anaesthetized rats. Cadmium acetate did not antagonize the pressor response of noradrenaline (4 micrograms i.v) which was blocked by Priscoline (10 mg/Kg i.v). Results of these experiments indicate that cadmium specifically blocks the initial transient pressor activity of clonidine. Cadmium is devoid of any adrenolytic activity. Cadmium clonidine interaction is independent of post synaptic adrenoceptor involvement.
Subject(s)
Acetates , Blood Pressure/drug effects , Cadmium/pharmacology , Clonidine/pharmacology , Animals , Dose-Response Relationship, Drug , Drug Interactions , Female , Male , Norepinephrine/pharmacology , RatsABSTRACT
Single exposure of endosulfan (5 mg/kg) to pigeons (Columbia livia) caused neuronal hyperexcitability as evidenced by spike discharges of 200-500 microV in the electroencephalograms (EEG) from the telencephalon and hyperstriatum, but there was no effect on the ectostriatal area. Cholinergic (muscarinic) receptor binding study using [3H]quinuclidinyl benzilate ([3H]QNB) as a specific ligand indicated that a single exposure to 5 mg/kg of endosulfan caused a significant increase (P less than 0.05) in [3H]QNB binding to the striatal membrane. Behavioral study further indicated that a single dose of 200 micrograms/kg of oxotremorine produced a significant induction in the tremor (P less than 0.01) in endosulfan-pretreated pigeons. The results of this behavioral and biochemical study indicate the involvement of a cholinergic (muscarinic) transmitter system in endosulfan-induced neurotoxicity.
Subject(s)
Brain/drug effects , Endosulfan/toxicity , Quinuclidines/metabolism , Quinuclidinyl Benzilate/metabolism , Receptors, Cholinergic/metabolism , Animals , Brain/metabolism , Columbidae , Electroencephalography , Female , Lethal Dose 50 , Male , Tremor/chemically inducedABSTRACT
In male Charles Foster rats, intracerebroventricular clonidine (0.2, 1.0, 10 mmol/l) caused dose dependent increase in the urine output and sodium excretion (P less than 0.01). Urinary creatinine excretion was decreased to a significant level (P less than 0.02). Urinary potassium excretion was increased but was not dose dependent. Maximal increase in the urine volume occurred during first hour of clonidine administration. Intraperitoneal administration of clonidine in similar molar concentration failed to produce changes in the urine volume. The results indicate that clonidine-induced diuresis is centrogenic and is attributed to the inhibition of the release of vasopressin from central hypothalamoneurohypophyseal axis.
Subject(s)
Clonidine/pharmacology , Kidney/drug effects , Animals , Clonidine/administration & dosage , Creatinine/urine , Electrolytes/urine , Injections, Intraventricular , Male , Rats , Rats, Inbred Strains , Sodium Chloride/pharmacologyABSTRACT
Normal and lesioned rats exposed to 3 mg/kg i.p. endosulfan for 10 subsequent days showed elevated foot-shock fighting behaviour in septal and nigral brain-lesioned animals. Increased ipsilateral circling was noticed in unilateral-nigral lesioned rats. A marked decrease in locomotor activity and no seizure pattern were recorded in rats treated with chlorpromazine (CPz). Electroencephalographic recording on the tenth day of endosulfan exposure showed high-voltage slow activity (HVSA) with occasional spindles and 5-6 Hz amplitude of 200 microV. In the treated rats an increase in the concentration of dopamine (DA) and a decrease in serotonin (5-HT) were recorded in amygdaloid, septal and nigral brain-lesioned rats.
Subject(s)
Aggression/drug effects , Agonistic Behavior/drug effects , Endosulfan/pharmacology , Neurotransmitter Agents/physiology , Animals , Chlorpromazine/pharmacology , Dopamine/metabolism , Electroencephalography , Female , Humans , Rats , Serotonin/metabolismABSTRACT
Cardiovascular responses to the intravenous (i.v.) and the intracerebroventricular (i.c.v.) administration of cadmium acetate were evaluated in rats anaesthetized with urethane. Cadmium acetate (1 mg/kg i.v.) caused an initial fall followed by a persistent rise in blood pressure. Cadmium acetate (1 microgram i.c.v.) produced a more marked hypertensive effect. In the spinal-transected rat, the effect of intravenous cadmium was reduced but the effect of intraventricularly administered cadmium was completely abolished. It is, therefore, suggested that both central and peripheral mechanisms are involved in the pressor response to cadmium exposure.
Subject(s)
Cadmium/pharmacology , Hemodynamics/drug effects , Animals , Blood Pressure/drug effects , Cadmium/administration & dosage , Heart Rate/drug effects , Injections, Intravenous , Injections, Intraventricular , Male , RatsABSTRACT
The synthesis and pharmacological activity of some 3-tertiary amino-1-aryloxy- or 1-aryl-, 1-thiophenoxy and 1-anilino-propan-2-ols and -propanes, particularly those derived from N-phenylpiperazines are described. Effect of substituents (nature/position) on the phenyl ring, the phenoxy ring as well as alteration in the hydroxylic function vis-à-vis the structure-activity relationships (SAR) are discussed. In general, the 1-aryloxy compounds have hypotensive activity--this being more pronounced in those carrying an o-substituent on the phenyl ring, while m and p-substituted derivatives have their effect primarily on the CNS. Variations in the phenoxy moiety do not significantly alter the intrinsic activity. The 1-aryl compounds, on the other hand, have significant CNS activity, which is markedly affected by the substituents on the 1-aryl residue.
Subject(s)
Propane/analogs & derivatives , Propanols , 1-Propanol/chemical synthesis , 1-Propanol/pharmacology , Animals , Anti-Inflammatory Agents , Anti-Inflammatory Agents, Non-Steroidal , Brain/drug effects , Female , Hemodynamics/drug effects , Male , Mice , Propane/chemical synthesis , Propane/pharmacology , Rats , Vasomotor System/drug effectsABSTRACT
Himachalol has been identified as the major antispasmodic constituent in the wood of Cedrus deodara. The pharmacological studies of himachalol on various isolated smooth muscles (guinea pig ileum, rabbit jejunum, rat uterus, and guinea pig seminal vesicle) and against different agonists (acetylcholine, histamine, serotonin, nicotine, and barium chloride) indicated spasmolytic activity similar to that of papaverine. It was a more potent antagonist of barium chloride-induced spasm of guinea pig ileum than papaverine but less effective in reverting a similar spasm of rabbit jejunum and had no relaxing effect alone. In the conscious immobilized cat, intragastric administration of himachalol or papaverine (100 mg/kg) produced equal inhibition of carbachol-induced spasm of the intestine, lasting about 2 hr, but himachalol had a faster onset of action. Himachalol was devoid of spasmolytic effect on the bronchial musculature of guinea pig but was 3.3 times more potent than papaverine in antagonizing epinephrine-induced contraction of the guinea pig seminal vesicle. Intravenous injection of himachalol (3-10 mg/kg) in the cat produced a dose-dependent fall in blood pressure and an increased femoral blood flow.
