An Investigation of the Adrenergic Blocking Action of Chlorpromazine

Gokhale, S. D.; Gulati, O. D.; Parikh, H. M.

doi:10.1111/j.1476-5381.1964.tb01606.x

Cited by 23 publications

(15 citation statements)

References 9 publications

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“…The increased pressor response in the rats treated with chlorpromazine-pentobarbital may be explained by the a-adrenergic blocking effect (Supek et al, 1962;Gokhale et al, 1964) and the potent inhibition of the central nervous system which occur in rats treated with these two agents in combination.…”

Section: Discussionmentioning

confidence: 99%

Effect of autonomic blocking agents on the cardiovascular effects of octapressin in the rat

Jong¹,

McLeod²

1967

European Journal of Pharmacology

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Effect of autonomic blocking agents on the cardiovascular effects of Octapressin in the rat, European J. Pharmacol. 1 (1967) 93-98.Cardiovascular effects of Octapressin were studied in anesthetized male albino rats. The effect of pretreatment with the following blocking agents was evaluated: atropine, phenoxybenzamine, propranolol, hexamethonium and chlorpromazine. A decrease in blood pressure and in heart rate was induced by phenoxybenzamine; propranolol treatment caused a decrease in heart rate and an increase in circulation time.Injections of 2, 6 and 18 mU Octapressin caused no changes in cardiac output or in central venous pressure. The increase in blood pressure following Octapressin was found to be dose-dependent in the saline-treated controls as well as in the rats pretreated with the autonomic blocking agents. The pressot response to Octapressin was increased by atropine, phenoxybenzamine, propranolol and chlorpromazine.From these data it is concluded that the increase in blood pressure following Octapressin is caused by an increase in vascular resistance in the systemic circulation.

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Section: Discussionmentioning

confidence: 99%

Effect of autonomic blocking agents on the cardiovascular effects of octapressin in the rat

Jong¹,

McLeod²

1967

European Journal of Pharmacology

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“…A similar suggestion had been made by other researchers regarding the uptake of labeled NE in peripheral tissues (22) and in the brain (1,23). However, as CPZ is an adrenergic blocking agent (16,17), the possibility remains that the enhancement of TB-induced NE depletion increases with hypersecretion of NE.…”

Section: Discussionmentioning

confidence: 83%

“…As CPZ has an adrenergic blocking effect (16,17), NE secretion was probably enhanced through a negative feedback control mechanism and the NE releasing action may have exceeded the suppression of NE decrease by its protection against the effect of RES on the granules. Yohimbine blocks presynaptic receptors, causing hypersecretion of NE (18,19).…”

Section: Discussionmentioning

confidence: 99%

Effects of Tricyclic Antidepressants on Tetrabenazine-Induced Depletion of Brain Monoamines In Rats. 1. Norepinephrine

Yoshizaki

Tonda

1980

Japanese Journal of Pharmacology

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Abstract-We studied the effects of tricyclic antidepressants on the tetrabenazine (TB)-induced depletion of brain norepinephrine (NE) using rats. The test drugs were generally administered orally 3 hr before and 2 mg; kg of TB or reserpine (RES) admin istered subcutaneously 2 fir before sacri ice. The TB-induced NE depletion was enhanced by pretreatment with desmethylimipramine (DM1, 25-100 nmg;kg), imi pramine (IM, 25-100 mg/kg), chlorimipramine (100 nmg!kg), maprotyrine (50 mg-'kg), amitriptyrine (50-100 mg 'kg), chlorpromazine (CPZ, 5-20 mg' kg i.p.) and anmphetanmine sulfate (10 mg; kg). DMI partially suppressed TB-induced NE depletion at 0.5 hr after TB administration. The RES-induced NE depletion was not enhanced with these drugs except for amphetamine.DMI, IM, and CPZ suppressed it instead. DM1 also enhanced the yohimbine (2 mg kg)-induced decrease. The brain NE content showed a tendency toward recovery 2 hr after TB administration, but approached the minimal level at 0.5 hr after TB administration or at 2 hr after RES administration in non-treated rats. In pargyline-pretreated rats, TB produced a decrease of brain NE with an increase of normetanephrine, while the action of RES was weaker than that of TB, up to 2 hr. These results suggest that enhancement of the TB-induced brain NE depletion by tricyclic antidepressants reflects the blockage of NE reuptake from the synaptic cleft.Tricyclic antidepressants inhibit norepinephrine (NE) reuptake at the neuronal cell membrane and this effect is considered to be an important action mechanism of these drugs(1-4). These drugs also antagonize various pharmacological effects of reserpine (RES) and tetrabenazine (TB) (5-7), and such effects have been used as indicators of the anti depressant action. Although the effect of the antidepressants on RES-induced changes of biogenic amine metabolism has been studied usually with desmethylimipramine (DMI) (8, 9), there are few reports in the literature on the TB-induced changes. We studied the acute effects of tricyclic antidepressants on the TB-induced and RES-induced depletion of brain NE and found that they enhance the former but not the latter. MATERIALS AND METHODSSeven-week-old reale Sprague-Dawley rats were used. The animals were exsanginated, the brain quickly removed, and the hemisphere which had been placed in acid-butanol or 0.4 N perchloric acid was homogenized and centrifuged. NE content of the acid-butanol extract was determined by the fluorimetric method of Chang (10) with slight modification and the normetanephrine (NM) content in the perchloric acid extract by the fluorimetric

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“…This would explain why in the rabbit, in which adrenaline does not produce vasodilatation, chlorpromazine antagonizes adrenaline and noradrenaline pressor activities to the same extent. Also on this basis, if the p-receptor effects of adrenaline were blocked by an appropriate antagonist such as dichloroisoprenaline, then the differential antagonism would be lost also in the cat, and Gokhale et al (1964) have now shown this to be so.…”

Section: Discussionmentioning

confidence: 97%

The Antiadrenaline Activity of Some Phenothiazine Derivatives

Webster

1965

British Journal of Pharmacology and Chemotherapy

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Phenothiazine derivatives are central nervous system depressants which apart from their wide use in psychiatry are of value in the relief of spasticity in conditions such as tetanus. In experimental tetanus in the rabbit it has been found that some phenothiazine derivatives diminish electromyographic activity in low doses but increase, or stimulate it, in high doses (Laurence & Webster, 1961). Although the mechanism of such stimulation has not been established it could be comparable to the Parkonisonian-like symptoms which often occur in man after relatively high doses of some phenothiazines.In view of the recent observation that there may be a depletion of dopamine in the central nervous system of Parkinsonian patients (Ehringer & Hornykiewicz, 1960) and since a possible correlation between experimental antitetanus and antiadrenaline activities has been indicated previously (Webster, 1961) it was decided to investigate more fully the relative antiadrenaline activity of a number of phenothiazine derivatives and to consider this property in relation to the central actions of these compounds. The results of such studies on rabbit and cat blood pressure are reported below. Quantitative studies were performed on rabbits since data on antitetanus activity had previously been obtained for this species. METHODS Animal preparationsAnaesthetized or spinal rabbits and cats were used. Before spinal section rabbits were anaesthetized with intravenous thiopentone sodium (Intraval) and cats with intraperitoneal pentobarbitone sodium (Nembutal). In both cases the following procedure was then adopted. The trachea was cannulated, both carotid arteries were tied and artificial ventilation was started. The dorsal surface of the spinal cord was exposed between the base of the skull and the atlas vertebra without laminectomy by bending the head forward and resecting the appropriate muscle layers. The exposed cord was then sectioned and cotton wool was pushed into the brain with a blunt instrument.Drug injections or adrenaline infusions were made through cannulae inserted into the femoral veins and blood pressure was recorded from a carotid artery with a mercury manometer. Assay procedureIn early experiments some indication of antiadrenaline activity was obtained by comparing the pressor response to adrenaline before and after giving a phenothiazine derivative.To obtain more quantitative comparisons of antiadrenaline activity the following course was followed. Adrenaline solution (50 jug/ml.) was infused at constant pressure at a rate of 3 to 10

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An Investigation of the Adrenergic Blocking Action of Chlorpromazine

Cited by 23 publications

References 9 publications

Effect of autonomic blocking agents on the cardiovascular effects of octapressin in the rat

Effect of autonomic blocking agents on the cardiovascular effects of octapressin in the rat

Effects of Tricyclic Antidepressants on Tetrabenazine-Induced Depletion of Brain Monoamines In Rats. 1. Norepinephrine

The Antiadrenaline Activity of Some Phenothiazine Derivatives

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