Intravenous Injection Of Chlorpromazine Research Articles

Dopamine receptor antagonists increase markedly the quantity of retrograde transport of HRP in the rat masseteric motoneuron

Horseradish peroxidase (HRP) was injected, bilaterally, into the rat masseter muscle, subsequent to an intramuscular or intraperitoneal injection of one of five dopamine antagonists (chlorpromazine and haloperidol as the D 1 and D 2 receptor antagonist, SCH 23390 as the specific D 1 receptor antagonist, sulpiride and domperidone as the specific D 2 receptor antagonist). Control rats received an injection of a corresponding vehicle solution. After a survival period of 16 h, the brainstem was cut into 60 μm cryosections and processed with the TMB technique. The amount of retrogradely transported HRP was quantitatively measured in terms of the amount of HRP reaction product present in the motoneuron by the method which we have developed using an image processing system combined with a light microscope and a TV camera. Chlorpromazine, haloperidol, SCH 23390 and sulpiride significantly raised the quantity of retrograde transport of HRP. On the contrary, domperidone which can not penetrate the blood-brain barrier showed no significant change in the amount of the retrograde transport. In addition, an intravenous injection of chlorpromazine (8 mg/kg) was found to increase the amplitude of monosynaptic masseteric reflex EMG activity evoked by stimulations of the mesencephalic trigeminal nucleus. These results suggest that a possible regulatory system involving the dopamine receptor in the uptake and retrograde transport of HRP from axon terminals to cell bodies of the masseteric motoneuron exists in higher order neurons which make synaptic contact with the motoneuron.

Effects of chlorpromazine on plasma glucose kinetics and concentration of long chain fatty acids in sheep

1. 1. Intravenous injection of chlorpromazine (CPZ) into sheep increased plasma glucose concentration from 3.4 to 5.6 mM and long chain fatty acid concentration from 0.29 to 0.40 mM within 10 min. Glucose returned to steady state within 210 min and fatty acid within 120 min. 2. 2. Plasma glucose kinetics were evaluated with a primed infusion of [6- 3H] d-glucose. 3. 3. The CPZ-induced hyperglycemia was caused by a large increase in glucose influx (from 8.6 to 70 μmol/min per kg) which was of short duration (20 min). 4. 4. The hyperglycemia was resolved by a moderate increase in glucose outflux (from 8.6 to 24 μmol/min per kg) which was of long duration (210 min).

Protection of chlorpromazine-induced arrhythmia by flavin-adenine-dinucleotide in canine heart.

To investigate the mechanism of chlorpromazine(CPZ)-induced ventricular arrhythmia, the changes in ventricular fibrillation threshold (VFT) were followed after intravenous injection of CPZ (1 mg/Kg) in dogs. Following injection, VFT was decreased to 56.6 +/- 5.4% (mean +/- SE) of the initial level. Since flavin-adenine-dinucleotide (FAD) combines specifically with CPZ in vitro, we investigate whether or not prior treatment with FAD prevents the CPZ effect. With FAD (2 mg/Kg), the CPZ-induced decrease in VFT was significantly cancelled (92.2 +/- 4.2% of the initial level). Mitochondria isolated from canine heart after CPZ injection showed a significant decrease in respiratory control index and ADP/O. Effects of CPZ on canine heart mitochondria were also well cancelled by prior administration of FAD. The findings suggest that the arrhythmogenic action of CPZ might be associated in part with impaired function of heart mitochondria. These results also suggest that FAD might be useful in the treatment of the cardiac disturbances associated with overdosage of CPZ.

Effect of chlorpromazine on the cerebral circulation

Intravenous injection of chlorpromazine in a dose of 2–3 mg/kg lowered the tone of the cerebral vessels and the general arterial pressure. The volume velocity of the cerebral blood flow increased if the arterial pressure remained stabilized or fell only moderately. In severe hypotension induced by chlorpromazine the cerebral blood flow decreased.

Studies on the mechanism controlling growth hormone release induced by chlorpromazine in the anesthetized rat.

In intact urethane-anesthetized rats, plasma growth hormone (GH) levels were low but increased significantly following intravenous injection of chlorpromazine. Plasma GH levels were significantly elevated in rats with hypothalamic cuts such as complete deafferentiation, anterior cut and antero-lateral cut, whereas plasma GH levels in rats with posterior cut or postero-lateral cut were not significantly different from those in rats with sham-operation. Intravenous injection of chlorpromazine caused an increase of plasma GH in rats with any type of hypothalamic cut. However, the maximum increments of plasma GH following chlorpromazine were larger in rats with antero-lateral cut and smaller in rats with posterior cut than in rats with sham-operation. These results suggest that extrahypothalamic inhibiting and stimulating neurons influence the regulatory mechanism of rat GH secretion through anterior and posterior routes to the hypothalamus respectively.

Effects of drugs influencing brain catecholamines on GH release in rats with hypothalamic surgery.

The effect of pretreatment with alpha-methyl-p-tyrosine (alpha-MT) on the basal levels of plasma growth hormone (GH) and the responses to chlorpromazine (CPZ) were investigated in urethane-anesthetized rats with either complete hypothalamic deafferentation (c.d.), hypothalamic ablation (H.A.) or sham operation (Sham). Basal GH levels were high in C.D. rats, intermediate in H.A. rats, and low in Sham rats without any pretreatment. Pretreatment with alpha-MT caused a significant increase in basal GH levels in both C.D. and Sham rats, but not in H.A. rats. GH release following the intravenous injection of CPZ, which was observed in C.D. and Sham rats without alpha-MT pretreatment, was blunted by treatment with alpha-MT. In H.A. rats CPZ failed to stimulate the secretion of GH regardless of alpha-MT pretreatment. Neither the injection of L-DOPA nor DL-DOPS affected basal GH levels in non-alpha-MT pretreated C.D. rats. However, plasma GH levels significantly decreased following the injection of L-DOPA, but not DL-DOPS, in C.D. rats pretreated with alpha-MT. These findings suggest that the injection of CPZ causes an enhancement of GH release by inhibiting the catecholaminergic (dopaminergic) mechanism, which is active within the basal medial hypothalamus (BMH) and plays an inhibitory role in GH secretion. They also suggest that the extrahypothalamic inhibitory neural pathway, which is connected to the BMH and is interrupted by hypothalamic deafferentation, is not catecholaminergic.

Effects of Hypothalamic Surgery and Somatostatin on Chlorpromazine-Induced Growth Hormone Release in Rats

Intravenous injection of chlorpromazine (100, 200, 500 µ.g/100 g body wt) produced a significant dose-related increase in plasma immunoreactive growth hormone (GH) in intact rats, in which basal plasma GH levels were low and stable under urethane anesthesia. Basal plasma GH levels were significantly elevated in rats with complete hypothalamic deafferentation or anterior hypothalamic cut, whereas there was no significant rise in plasma GH in rats with a posterior hypothalamic cut. Increases in plasma GH induced by chlorpromazine (200 µg/100 g body wt iv) were also observed in rats with complete deafferentation, or anterior or posteriorcuts of the hypothalamus. Chlorpromazine did not cause any significant increments in plasma GH in rats with extensive hypothalamic destruction. Synthetic somatostatin (5 µg/100 g body wt iv) significantly suppressed plasma GH response to chlorpromazine (100 µg/100 g body wt iv). These results suggest that rat GH release can be stimulated by chlorpromazine influencing the hypo...

Effect of psychotropic drugs on phosphodiesterase and cyclic AMP level in rat brain in vivo

Recently, several psychotropic drugs have been shown to change cyclic AMP metabolism in brain. In the present study the effect of neuroleptics and antidepressants on phosphodiesterase activity in vitro and on cyclic AMP content of rat brain in vivo was examined. Chlorpromazine, triflupromazine and chlorprothixene inhibited the phosphodiesterase in a non-competitive manner, whereas imipramine, desipramine and amitryptiline proved to be competitive inhibitors. Haloperidol had virtually no effect on phosphodiesterase activity. The content of cyclic AMP was determined in tissue cylinders of rat forebrain obtained by biopsy puncture and immersed in liquid nitrogen within 3 sec. Following intravenous injection of chlorpromazine (5 mg/kg) the cyclic AMP content was elevated 2.5-fold within 1 min and had declined to control values after 3–5 min. Pretreatment with theophylline (10 mg/kg i.p.) which alone did not influence cyclic AMP levels completely prevented the chlorpromazine induced increase of cyclic AMP in brain but did not change the drug-induced effects on behaviour. Desipramine (10 mg/kg) and haloperidol (0.25 mg/kg) also elevated the cyclic AMP content in rat brain, but this effect was only partly antagonized by theophylline (20 mg/kg). Chlorpromazine (5 mg/kg i.v.) did not alter cyclic AMP levels in heart muscle, kidney and adipose tissue, but elevated the cyclic AMP concentration of the liver 2-fold. Our results suggest that the inhibition of phosphodiesterase by psychotropic drugs is obviously of minor importance for the observed accumulation of cyclic AMP and is not directly related to the psychopharmacological effects of these agents.

Study of the mechanism of hyperglycemia and arterial hypertension produced by venom of the scorpion, in the dog

In the present paper we studied the mechanism of the hyperglycemia and hypertension evoked by the intravenous injection of scorpion venom (Tityus bahiensis) in the dog. We used 34 dogs, of both sex, weighing between 4.3 to 22 kg. These animals were divided in 3 groups and the following experiments were performed: in the first group (8 dogs) the animals were adrenalectomized after the intravenous injection of chlorpromazine; in the second group (16 dogs) the animals were injected with ganglionic blocking drugs (9.295 Ciba and hexamethonium); in the third group (10 dogs) the naimals were injected with dibenamine, and in 3 of them the adrenal glands were removed. The dogs of each group were injected intravenously with aqueous extract of 2 telsons of scorpion/kg; the average weight of each telson was 6,5 mg. The following results were obtained: 1) The hyperglycemia evoked by scorpion venom, in adrenalectomized dogs, was inhibited by chlorpromazine; 2) Ganglionic blocking drugs (9.295 Ciba and hexamthonium) were inefective as far as the hyperglycemic and pressor effects of venom are concerned; 3) In the animals treated with dibenamine, the venom produced a fall in blood pressure, both in the controle and in the adrenalectomized. The present experiments suggest that the scorpion venom has, besides the central action already described by other investigators, an adrenergic action, very similar to the adrenaline. On basis of our experiments we think that the adrenergic action is responsible, in part, by the productrion of hyperglycemia and hypertension.

Zum Mechanismus des reflektorischen Atemstillstandes nach intraven�ser Injektion von Chlorpromazin

Transient stop of respiration in exspiratory position can be produced in cats by intravenous injection of chlorpromazine, promethazine, and diethazine. The effect is dependend on the velocity of injection and on the concentration of the injected solution. Furthermore, it is most powerfull after administration into the arteria pulmonalis, but cannot be recognised after injection into the vena pulmonalis or into the bulbus aortae. It is abolished by vagotomia, but not by cooling both vagi to 6°C. Records of afferent vagal impulses at this temperature don't provide evidence for activation of lung stretch receptors. The alterations of blood pressure in the arteria et vena pulmonalis develop slowly and are only small. Therefore the chemosensible pulmonary vascular receptors are supposed to be chiefly involved in the reflectory stop of respiration after chlorpromazine, promethazine, and diethazine.

Mechanisms of immediate respiratory responses to chlorpromazine.

Following the intravenous injection of chlorpromazine (5 mg/kg) in dogs anesthetized with Pentothal-chloralose, respiratory inhibition occurs followed by stimulation. A fall in arterial blood pressure accompanies the respiratory responses. The evidence indicates that a reflex is involved with receptors for the inhibitory response and at least the major portion of the stimulation located in the thorax with afferent pathways in the vagus nerves. The inhibition and stimulation persist when the arterial blood pressure is compensated. The inhibition and most of the stimulation are eliminated by vagotomy. It is suggested that the respiratory responses are primarily due to the activation of chemical-sensitive receptors. A portion of the stimulation may be related to the fall in blood pressure.

Effect of chlorpromazine upon epileptic and normal monkeys.

Conclusions1. The rapid intravenous administration of chlorpromazine (2-10 mg/kg) to epileptic and normal monkeys produced prompt profound behavioral changes characterized by hypokinesia, flaccidity, diminished responsiveness, reduced aggressiveness, lethargy and somnolence. 2. High amplitude slow wave activity (2-5 second) became dominant in the EEG up to several hours after intravenous injection of chlorpromazine; epileptic monkeys showed, in addition, increased high amplitude spike and sharp wave forms. 3. Epileptic monkeys under the acute influence of chlorpromazine retained their clinical convulsive responsiveness to intramuscular Met-razol (16 mg/kg or less). Clinical epileptic response to vigorous prodding was not significantly changed. 4. Normal control monkeys under the acute influence of chlorpromazine did not exhibit clinical convulsions and remained refractory to treatment with intramuscular Metrazol (32 mg/kg) and to vigorous prodding stimulation.

EXTREME TACHYCARDIA FOLLOWING THE INTRAVENOUS INJECTION OF CHLORPROMAZINE

Medical Journal of AustraliaVolume 2, Issue 20 p. 802-803 Correspondence EXTREME TACHYCARDIA FOLLOWING THE INTRAVENOUS INJECTION OF CHLORPROMAZINE First published: 01 November 1954 https://doi.org/10.5694/j.1326-5377.1954.tb66987.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume2, Issue20November 1954Pages 802-803 RelatedInformation