The Journal of pharmacology and experimental therapeutics
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J. Pharmacol. Exp. Ther. · Feb 1976
In vivo actions of clozapine and haloperidol on the turnover rate of acetylcholine in rat striatum.
We have measured acetylcholine (ACh) content and turnover rate (TRACh) in striatum and cortex of rats receiving haloperidol and clozapine i.p. Both clozapine (30 mumol/kg) and haloperidol (10 mumol/kg) reverse the decrease in striatal TRACh elicited by apomorphine (11 mumol/kg) while each antipsychotic affects the steady state and the TRACh in striatum differently. Haloperidol fails to change striatal ACh content but increases the TRACh; chozapine (15 and 30 mumol/kg) neither decreases the content of ACh nor changes the TRACh in striatum. ⋯ Moreover, clozapine and benztropine reverse the increase in striatal TRACh elicited by haloperidol. The increase in striatal TRACh elicited by haloperidol could be of value to explain the extrapyramidal action of this drug. The anticholinergic action of clozapine could explain the absence of extrapyramidal side effects observed with this drug.
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J. Pharmacol. Exp. Ther. · Jan 1976
Comparative StudyEffect of experimental azotemia on renal clearance of furosemide in the dog.
The clearance of furosemide (F), whose renal tubular transport shares the classical characteristics of the organic acid system, was determined in dogs with varying degrees of azotemia and compared with tetraethylammonium (TEA), an organic base. Two normal and eight azotemic dogs [blood urea nitrogen (BUN), 12-273] were studied. Azotemia was produced by bilateral uretero-venous anastomoses. ⋯ After acute administration of exogenous urea to two dogs (BUN 170 and 253) CTEA/CF was unrelated to BUN. Thus, the CF decreases proportionately with progressive azotemia and is not related to RBF, exogenous urea or metabolite. This suppression of renal tubular secretion of furosemide may partially account for reduced therapeutic efficacy of furosemide in azotemia.
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J. Pharmacol. Exp. Ther. · Dec 1975
The depressant effect of halothane and sodium thiopental on the spontaneous and evoked activity of dorsal horn cells: lamina specificity, time course and dose dependence.
The effects of halothane and sodium thiopental on dorsal horn cell unit activity were studied in the lumbar spinal cord of decerebrate, low thoracic spinal cats. Both halothane (0.5, 1 and 1.5%) and sodium thiopental (2.5, 5 and 10 mg/kg) depressed, in a dose-dependent manner, the spontaneous firing frequency of cells in Rexed laminae I, V and VI and the evoked firing frequency of cells in laminae I and V. ⋯ The recovery of cell activity occurred within 15 to 30 minutes after discontinuation of halothane and within 10 to 30 minutes after intravenous administration of sodium thiopental. The depressive effect of halothane and sodium thiopental, both primarily hypnotic anesthetics, on lamina VI cells is in contrast to our previous finding that morphine sulfate, nitrous oxide and ketamine hydrochloride, primarily analgesic agents, had no significant effect on this lamina.
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J. Pharmacol. Exp. Ther. · May 1975
Comparative StudyRate-dependent Effects of drugs. II. effects of some major tranquilizers on multiple fixed-ratio, fixed-interval schedule performance.
The effects of promazine, chlorpromazine, triflupromazine, prochlorperazine, trifluoperazine, perphenazine, fluphenazine, haloperidol, benzquinamide, tetrabenazine and chlorprothixene were determined on the rate of conditioned key pecking of pigeons under a multiple fixed-ratio 30, fixed-interval 5-minute schedule of food presentation. Chlorpromazine, prochlorperazine, perphenazine, chlorprothixene and tetrabenazine decreased responding relatively more within the fixed-interval component than within the fixed-ratio component and also produced rate-dependent effects within the fixed interval component, increasing the low rates of responding early in the fixed-interval but decreasing the high rates of responding in the terminal parts of the fixed interval. Triflupromazine, trifluoperazine, fluphenazine and haloperidol also decreased responding relatively more within the fixed-interval component than within the fixed-ratio component, but did not produce rate-dependent effects within the fixed-interval component. ⋯ Promazine and benzquinamide decreased responding relatively more within the fixed-ratio component than within the fixed-interval component and also produced rate-dependent effects within the fixed-interval component. There was a structure-activity relationship between the chemical group on the benzene ring of the phenothiazine nucleus and the rate-dependent effect on responding within the fixed-interval component. Phenothiazines with a hydrogen or chlorine group on the benzene ring produced a rate-dependent effect on responding within the fixed interval, while phenothiazines with a trifluoromethyl group on the benzene ring did not produce a rate-dependent effect on responding within the fixed interval.