Neuropharmacological Aspects of Reserpine

Schneider, Jürg; Plummer, A. J.; Earl, Alfred E.; Gaunt, Richard A.

doi:10.1111/j.1749-6632.1955.tb42448.x

Cited by 50 publications

(8 citation statements)

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“…Angelucci (4) has reported that both chlorpromazine and reserpine inhibit spinal reflexes in the frog; Dasgupta and Werner(5) found that chlorpromazine completely suppresses the crossed extensor reflex in decerebrate cats. On the other hand, Preston (6) has reported that doses of chlorpromazine causing obvious changes in the behavior of cats produce no observable alterations in monosynaptic and polysynaptic reflex arcs of the spinal cord: doses of 5 mg/kg of reserpine were found to increase the magnitude of the monosynaptic spike of the ventral root potential without significant change in the polysynaptic potentials (7). Our results fall between these two extremes: we find that both chlorpromazine and reserpine decrease fairly specifically the magnitude of the monosynaptic potential, which would be expected to mean that these drugs inhibit simple reflexes like the knee jerk but not more complex ones.…”

Section: Actions Of Chlorpromazine and Of Reserpine On Spinal Reflexmentioning

confidence: 96%

Actions of Chlorpromazine and of Reserpine on Spinal Reflex Activity in the Cat

Krivoy

1957

Experimental Biology and Medicine

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These experiments are based on the finding that doses of chlorpromazine that do not modify conduction depress transmission in the inferior mesenteric ganglion of the cat (Krivoy, unpublished). If the synapse in the spinal cord resembles the ganglionic synapse, chlorpromazine should modify transmission in the spinal cord also. The present experiments were designed to study this possibility.Methods. In one preparation ( 1 ) , laminectomy was performed at the level of the last lumbar or first sacral segment to expose homolateral dorsal and ventral roots from the same spinal segment. The roots were mounted on electrodes. The skin edges around the incision were elevated and the trough so formed was filled with mineral oil maintained at 37°C. A second method(2) consisted of stimulating and recording through 2 pairs of electrodes applied to the same sciatic nerve, which had been cut distally. Electrical equipment and methods of recording have been described previously( 3), only the AC amplifier being used in these experiments. Bright silver electrodes were used with spinal roots, whereas wick electrodes were used for sciatic nerve experiments. The dorsal root or sciatic nerve was stimulated with biphasic pulses a t a frequency varying from .S-l/sec. with a stimulus duration of .l-.5 msec. Except where noted, stimulus intensity was SO-SO% maximal. All stimulus parameters were main-

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Section: Actions Of Chlorpromazine and Of Reserpine On Spinal Reflexmentioning

confidence: 96%

Actions of Chlorpromazine and of Reserpine on Spinal Reflex Activity in the Cat

Krivoy

1957

Experimental Biology and Medicine

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“…Thus reselpine, rescinnamine, and deserpidine, in contrast to chlorpromazine and other drugs of Group 1, appear to have no direct action on the reticular activating system of the brain stem nor do they block the effects of afferent nerve stimulation on this system but appear merely to modify these influences. The concept of an action at a cortical level, producing an increase in " cortical inhibition of diencephalic centres " (Schneider, Plummer, Earl, and Gaunt, 1955), would not conflict with this conclusion. In fact, it may offer a possible explanation of the slight increase in the threshold for sensory induced arousal seen in previous experiments (Key and Bradley, 1958) since the cortex is known to exert some influence upon conduction within the brain stem reticular formation (French, Hernandez-Peon and Livingston, 1955;Adey, Segundo, and Livingston, 1957).…”

Section: Benactyzinementioning

confidence: 96%

A Comparative Study of the Effects of Drugs on the Arousal System of the Brain

Bradley¹,

Key²

1959

British Journal of Pharmacology and Chemotherapy

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The effects of twelve drugs, eleven of which are reported to be tranquillizers, have been studied in relation to thresholds for arousal produced both by direct stimulation of the brain stem reticular formation and also by afferent nerve stimulation. The drugs can be grouped according to whether (a) like chlorpromazine they produce a slight rise in thresholds for brain stem stimulation and block sensory-induced arousal, (b) cause dissociation between behaviour and electrical activity of the brain, (c) have no effects on thresholds for brain stem stimulation and only slight effects on afferent nerve-induced arousal or (d) have no effect on arousal responses at all.The effects of twelve different drugs on arousal responses have been investigated. Most of the drugs chosen for the present study have been classed as tranquillizers on the basis of their clinical effects although there are differing reports regarding the clinical efficacy of some of them. It is, however, not our intention to discuss this question here.Much of the early experimental work with chlorpromazine suggested an action at the level of the reticular activating system of the brain stem (Terzian, 1952;Longo, von Berger, and Bovet, 1954;Hiebel, Bonvallet, and Dell, 1954) and further investigations (Bradley and Hance, 1957) confirmed this. The drug blocked the behavioural and electroencephalographic effects of arousal stimuli, both in the conscious unrestrained animal and in acute preparations (encgphale isokg) and also blocked the excitant action of amphetamine, which is itself thought to act at the brain stem level (Bradley and Elkes, 1957). A more detailed study of the effects of drugs on arousal responses (Bradley and Key, 1958) demonstrated that chlorpromazine had little depressant action on the brain stem activating system itself but produced a selective blocking of the afferent influences on this system. This led to the hypothesis that chlorpromazine might act by depressing the collateral inflow into the reticular formation from the afferent pathways. So far no evidence has been produced which suggests that this hypothesis is wrong and further studies support it (Bradley, 1957;Key and Bradley, 1958). On the other hand we have not attempted to suggest that this particular central action of chlorpromazine is solely responsible for its clinical properties or that it is the only action of this drug on the central nervous system. The tranquillizers form a group which, for almost all investigated properties, is so heterogeneous that we thought it might be worth while to examine the effects of a number of these compounds upon the arousal system. In this way it should be possible to see how far the hypothesis which has been elaborated to explain the action of chlorpromazine in neurophysiological terms might be extended to include other tranquillizers. METHODSExperiments were carried out on 56 adult cats, all of which were encephale isolW preparations (Bremer, 1936). The animals were prepared under ether anaesthesia using a technique which has been des...

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“…Chlorpromazine suppresses oestrus in rats (Das Gupta, 1955) when given intraperitoneally in a dose of 10 mg/kg, and can also interfere with menstruation in women (Ayd, 1959). Since the tranquillizers act on the hypothalamus (Das Gupta, Mukherjee & Werner, 1954;Schneider, Plummer, Earl & Gaunt, 1955;Tangri & Bhargava, 1960), the possibility was considered that in a sufficient dose all tranquillizers would affect the oestrus as well as the menstrual cycle. In the investigation described here, the effects of a number of phenothiazine tranquillizers were studied on albino mice to test this hypothesis.…”

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confidence: 99%