Effects of chlorpromazine on some motor reflexes

Hudson, Roy D.; Domino, Edward F.

doi:10.1016/0028-3908(63)90017-0

Cited by 14 publications

(4 citation statements)

References 33 publications

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“…The antagonism of the decerebrate rigidity by the compound is in agreement with the finding of Stille et al (1). Similar results have been reported with chlorpromazine by Hudson and Domino (13). Haloperidol, however, has been reported to inhibit the facilitation and potentiate the inhibition of the PR due to stimulation of reticular forma tion (5).…”

Section: Methodssupporting

confidence: 89%

EFFECT OF 2-CHLORO-11 (4′-METHYL) PIPERAZINO-DIBENZO (b,f) (1,4)-THIAZEPINE ON SOMATIC REFLEXES IN CAT

Sharma

Srimal

1969

Japanese Journal of Pharmacology

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Pharmacological properties of a potent neuroleptic agent, 2-chloro-ll-(4'-methyl) piperazino-dibenzo (b, f) (1, 4)-thiazepine (HF-2159) have been described by Stille et al. (1). Its profile of activity is in between chlorpromazine and haloperidol, both of which have marked effects on somatic reflexes (2-6). The present investigation has been under taken to study the effect of HF-2159 on the somatic reflexes integrated at the spinal and the supraspinal level. Preliminary results of this study have appeared (7). METHODSThe experiments were conducted in adult cats (2.5 to 4.0 kg) of either sex. The ani mals were anaesthetized with chloralose (80 mg/kg i.v.), except when they were decere brated or made spinal (C7). In the latter cases surgery was done under ether anaesthe sia. The reflexes were elicited at least one hour after stopping ether. All the animals were maintained on artificial positive pressure ventilation and were vagotomized.Effect of the compound on neuromuscular transmission was studied by recording the contractions of the gastrocnemius muscle due to stimulation (1.5 V, 0.5 msec duration and 12 pulses per minute) of distal end of the cut sciatic nerve. The muscle was also stimulat ed directly at regular intervals to note the effect on the contractility of the muscle. Patellar reflex (PR) was elicited by tapping the tendon of the quadriceps muscle every 10 seconds, by means of an electromagnetic hammer. The movement of the limb was recorded on a kymograph through a system of pulleys (8). Monosynaptic inhibition of this reflex was obtained by stimulating the ipsilateral sciatic nerve, the contralateral nerve being cut (9). The polysynaptic facilitation and inhibition of the PR were obtained by electrical stimulation of the cut central end of the contralateral sciatic nerve or the brain stem reticular formation (10). A concentric needle electrode was used to stimulate the reticular formation. The flexor reflex was elicited by stimulating the cut central end of the sciatic nerve, distal to the origin of the nerve to the tibialis anterior muscle. Contrac tions of the tibialis anterior muscle were recorded on the kymograph. The crossed exten sor reflex was also recorded along with the PR of the contralateral limb. The linguoman dibular flexor reflex was elicited by stimulating the root of the tongue, by means of two needle electrodes, and recording the movement of the lower jaw (11).* Communication number

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Section: Methodssupporting

confidence: 89%

EFFECT OF 2-CHLORO-11 (4′-METHYL) PIPERAZINO-DIBENZO (b,f) (1,4)-THIAZEPINE ON SOMATIC REFLEXES IN CAT

Sharma

Srimal

1969

Japanese Journal of Pharmacology

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“…The cat's head was stereotaxically fixed and bipolar concentric stimulating electrodes were acutely implanted in the mesencephalic facilitatory (BF) and medullary inhibitory (BI) reticular formation. (For details see HUDSON and DOMINO, 1963). Stimulation of these sites for a period of 5 set at a frequency of 100 c/s with a pulse duration of 1 msec produced patellar reflex increment and decrement respectively.…”

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confidence: 99%

Central muscle relaxant effects of diazepam

Hudson

Wolpert

1970

Neuropharmacology

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Motor depressant effects of diazepam were studied in the intact, decerebrate and high spinal cat. Diazepam (0.125516 mg/kg, i.v.) produced a depression of both the patellar and linguomandibular reflexes in the intact cat. In the high spinal (Cl) cat only the linguomandibular reflex was depressed. Facilitation and inhibition of the patellar reflex elicited in both intact and high spinal (Cl) cats were reduced by diazepam. No depression was observed in the in viva neuromuscular preparation of the tibialis anticus muscle. Small doses of diazepam (0.125 mg/kg, i.v.) abolished the rigidity of the mid-collicular decerebrate cat.Mean arterial blood pressure was initially depressed in all animals (0.125-2 mg/kg) with an intact medullary vasomotor outflow. Larger doses (4-16 mg/kg) tended to return the blood pressure toward control levels.The present study presents evidence for both a brain stem reticular and a spinal cord site of action of diazepam on motor systems. Possible mechanisms of action of diazepam on motor systems are discussed. DIAZEPAM, a 1,4_benzodiazepine derivative, has been clinically and experimentally demonstrated to possess skeletal muscle relaxant properties (RANDALL ef al., 1961; SCHALLEK et al., 1964; SVENS~N and GORDON, 1965).HERNANDEZ-PEON et al. (1964) suggested that diazepam may selectively depress reticular facilitatory neurons involved in regulation of postural tone. Evidence for such a brain stem site of action of diazepam was demonstrated by NCAI et al. (1966) and PRZYBYLA and WANG (1968). OLAFSON er al. (1964) postulated that diazepam might have a specific spinal cord site and mechanism ofaction due to its potency in the treatment of the rare "stiffman" syndrome. This syndrome was theorized to be due to a pathophysiologic block of the spinal synaptic junction between interneurons of the inhibitory pathways and the motoneuron.The purpose of the present investigation is to further elucidate the central effects of diazepam on motor function in the experimental cat. METHODSFifty adult cats of both sexes, ranging from 2.5 to 4.6 kg were used in this investigation. Intact, mid-collicular decerebrate and high spinal (Cl) preparations were utilized. Site of action of diazepam 483Atti. Sot. med C&r. Padova i2: 5-16. STELLA, G. (1944b). Influenza del cerveletto sulla rigidit& da decercbrazione. Atti. Sot. medChir.Paduva22: 17-21.

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“…Henatsch & Ingvar (1956), however, used cats decerebrated by the anaemic method of Pollock & Davis (1930), in which rigidity is maintained by a-activity, and their results are probably therefore not comparable. Since in our preparations both tonic and reflex- induced a-discharges were abolished by chlorpromazine, it cannot be concluded that chlorpromazine has no effect on the a-motoneurone as proposed by Henatsch & Ingvar (1956) and Hudson & Domino (1963). Muscle relaxation produced by mephenesin could be due either to a direct depression of the a-motoneurone or to a reduction in its excitability by removal of interneuronal influences. The former seems unlikely since mephenesin does not abolish all voluntary movement, and the monosynaptic stretch reflex has generally been found to be unaltered.…”

Section: Discussionmentioning

confidence: 48%

“…Chlorpromazine also retained an effect on a-discharges after the preparation of a number of ventral roots for recording, which automatically cuts down the y-influence to the spindles, and after the splitting down of the motor nerve which greatly reduces the afferent input to the cord. The observations by other workers that chlorpromazine can reduce dorsal root or motor nerve evoked reflex discharges (Hudson & Domino, 1963) when presumably some of the afferent input must have been reduced by the requirements of the preparation also implies a direct effect of chlorpromazine on the a-system. Nevertheless, the main effect of chlorpromazine is presumably a depression of the y-motor system.…”

Section: Discussionmentioning

confidence: 87%

Effects of Mephenesin and Chlorpromazine on Motor Nerve Discharges in the Rabbit

Webster

1965

British Journal of Pharmacology and Chemotherapy

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Although many hypnotic, sedative and tranquillizing drugs are to some extpnt centrally acting muscle relaxants, mephenesin is perhaps the only drug that has this effect as a primary action. It is generally believed to achieve this by blocking transmission at spinal interneurones, since it blocks polysynaptic but not monosynaptic reflexes. Chlorpromazine has also been found to produce muscular relaxation in both experimental and clinical tetanus although its mechanism of action probably differs from that of mephenesin (Webster, 1961).Muscle tone depends not only on the discharge of a-motoneurones to the muscle extrafusal fibres, but also on the reflex activation of this pathway through monosynaptic excitation of the motoneurone by impulses from the muscle spindles (also called intrafusal fibres), which are propioceptive receptors within the muscle itself. The muscle spindles are in turn activated by impulses in smaller (y) motor nerves and their state of excitability, and consequently the input that they send into the cord, depends on the degree of y-innervation and the level of activity within the extrapyramidal system of which it forms part.The effect on these two motor systems of mephenesin and chlorpromazine, in doses known to produce equivalent muscular relaxation (Webster, 1961), has been studied using discharges from a-and y-motoneurones, recorded in ventral root or motor nerve filaments; and spindle discharges, recorded in dorsal root filaments of the decerebrate rabbit. METHODSAll experiments were performed on decerebrate rabbits. Surgical anaesthesia was induced with thiopentone sodium (25 mg/kg), administered into a marginal ear vein, and maintained with ether. The trachea was cannulated, both carotid arteries were tied and a polyethylene cannula was inserted into the right femoral vein for drug injections. PreparationsVentral root. Clamps were inserted into the lower part of each femur and the extremity of each tibia. The animal was then rigidly fixed to the myograph stand, additional clamps being placed on the spinous process of the 4th lumbar vertebra and across the two ischial tuberosities of the pelvic girdle. The head was held firmly in a clamp and the fore-limbs tied securely. Laminectomy was performed from L5/6 to S3 and the sural nerve was exposed for stimulation. Dorsal root. The animal was fixed as above but the left hind-limb was extensively denervated. The femoral and obturator nerves were first cut and then, through an incision in the left popliteal fossa, all branches of the sciatic and popliteal nerves were cut, apart from those to plantaris and medial gastro-

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Effects of chlorpromazine on some motor reflexes

Cited by 14 publications

References 33 publications

EFFECT OF 2-CHLORO-11 (4′-METHYL) PIPERAZINO-DIBENZO (b,f) (1,4)-THIAZEPINE ON SOMATIC REFLEXES IN CAT

EFFECT OF 2-CHLORO-11 (4′-METHYL) PIPERAZINO-DIBENZO (b,f) (1,4)-THIAZEPINE ON SOMATIC REFLEXES IN CAT

Central muscle relaxant effects of diazepam

Effects of Mephenesin and Chlorpromazine on Motor Nerve Discharges in the Rabbit

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