Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026838 (spasticity)
 6,471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clonidine tablets have been used in the past for treatment of spasticity with some success. The use of clonidine, however, has been limited by adverse effects, mainly hypotension. Over a two-year period, 17 patients were started on clonidine transdermal delivery system. They were followed for up to 18 months. Twelve of the 17 patients had a beneficial response and have continued on the patch. In ten of these 12 patients, other antispasticity drugs were either reduced or discontinued. In another three of the 17 patients, the response was good, but the patch was discontinued. No patient demonstrated persistent problematic hypotension. Clonidine Transdermal Patch appears to be an effective treatment for spasticity after a spinal cord injury. Adverse effects appear to be minimized using this mode of delivery.
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PMID:Clonidine transdermal system for treatment of spasticity in spinal cord injury. 151 97

When administered systemically to spinalized animals, clonidine, the prototypic alpha 2 adrenergic receptor agonist, purportedly acts at spinal sites to suppress motor responses related to painful peripheral and vesical stimulation and spasticity, and to improve vesicourethral coordination. Hence, the action of clonidine (400 micrograms in three divided doses in a 16-hour span) on spinal vesical and somatic reflexes was examined in five patients with suprasacral spinal cord lesions by assessing volume-induced micturition reflexes and limb motor discharges that occurred spontaneously or were elicited by noxious and nonnoxious cutaneous stimulation. Clonidine caused a significant reduction in (1) blood pressure, (2) amplitude of detrusor contraction, and (3) vesical external urethral sphincter dyssynergia. Limb motor electromyography discharges were not markedly attenuated, although spatiotemporal changes (eg, irradiation, after-discharges) were observed in some of the patients. The results are ascribed to binding to spinal cord alpha 2 adrenergic receptors located on segmental and intersegmental (propriospinal) interneurons, released from descending inhibition, with greater motor system specificity on striated sphincter innervation. Clonidine may be clinically effective in the treatment of hyperactive micturition reflexes in patients with chronic spinal lesions.
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PMID:Clonidine inhibits vesico-sphincter reflexes in patients with chronic spinal lesions. 205 29

We have investigated the influence on the excitability of lumbar motoneurons of 5-hydroxytryptamine (5-HT), substance P and thyrotropin releasing hormone (TRH), three substances which coexist in the same bulbospinal descending pathway and end in large part around motoneurons. We have also studied the effect of clonidine, an alpha 2 noradrenergic agonist. This was done in spinalized rats (T5) treated three weeks before with 5-7-dihydroxytryptamine. Under those circumstances 5-HTP (I.P.), 5-HT (intrathecally) TRH (I.P. or I.T.) and substance P (I.T.) all elicited a strong excitation of motoneurons as measured by integrated EMG of the hindlimb muscles. Substance P reduced by almost half the subsequent response to 5-HTP, 1 hour and 24 hours later. TRH given acutely did not modify the response to 5-HTP but given chronically for twenty one days by means of Alzet minipump, markedly increased the response to 5-HTP. Clonidine by itself decreased the excitability of motoneurons and antagonized the excitatory effect of 5-HTP and TRH. In a pilot trial, cyproheptadine, a 5-HT antagonist was shown to decrease the manifestations of spasticity in patients with a partial spinal lesion. Clonidine also appears to be of potential use in the treatment of spasticity.
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PMID:Action of 5-hydroxytryptamine, substance P, thyrotropin-releasing hormone and clonidine on motoneurone excitability. 244 57

In a single blind study of 6 spinal cord injured (SCI) men, the effects of clonidine, a selective alpha-2 adrenergic agonist, on spasticity were compared to diazepam and placebo. Since a potential side-effect of clonidine is postural hypotension, a combination of clonidine and desipramine was also tested. Vibration of the leg will inhibit the H reflex in a normal subject; whereas, this inhibition is markedly reduced in SCI patients with spasticity. A vibratory inhibition index (VII) was derived for each treatment. The pre-treatment VII was 92.08 +/- 3.15%; for SCI subjects, compared to 46.5 +/- 7.7% for 6 normal subjects. Clonidine significantly reduced the mean index of SCI patients to 59.42 +/- 3.91% (p less than 0.001). The VII for placebo, diazepam and the clonidine-desipramine combination were not statistically different than the pre-treatment values in SCI patients. In conclusion, clonidine has an anti-spasticity effect in SCI patients, both subjectively, and objectively, in terms of vibratory inhibition of the H reflex.
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PMID:Reflex changes induced by clonidine in spinal cord injured patients. 257 Nov 16

In a dose of 0.1 mg/kg clonidine, an alpha-2 receptor agonist, depressed the spontaneous EMG activity of the biceps and quadriceps femoris in chronically-spinalized rats. It also antagonized in a dose-dependent manner the stimulating effect of 5-hydroxytryptophan (5-HTP, 100 mg/kg). Doses of more than 0.1 mg/kg were less potent in antagonizing the effect of 5-HTP. Clonidine reduced the tonic activity of the hindlimb muscles but allowed walking movements. The depressant effect of clonidine in animals pretreated with 5-HTP was prevented by yohimbine (1.25 mg/kg), while the depressant action of the serotonin antagonist, cyproheptadine was not. In chronically-spinalized rats, clonidine (0.1 mg/kg) increased the threshold of electrically-induced flexor and extensor reflexes and decreased their amplitude. No significant modification of reflexes was seen with this dose 24 hr after spinalization. Thus, clonidine in doses of 0.1 mg/kg or less reduced directly or indirectly the excitability of motoneurons. Clonidine may prove to be a useful therapeutic adjunct in the treatment of spasticity.
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PMID:Effect of clonidine on motoneuron excitability in spinalized rats. 300 4

Clonidine was used as an adjunct to baclofen in 55 patients with spasticity due to spinal cord injury. Dosage was held at the minimum effect amount for those who responded. No effect was seen in 24 patients (44%), although 31 (56%) benefitted from the drug. Patients were grouped as quadriplegics or paraplegics, having complete or incomplete lesions. Of all quadriplegics, seven of 11 complete (64%) and 17 of 25 incomplete patients (68%) responded; among the paraplegics, six of 15 complete (40%) and one of four incomplete patients (25%) improved. Side effects were limited to postural hypotension necessitating reduction in dosage in three patients that were successfully treated; in the unsuccessfully treated group, one patient had insomnia, one had dizziness, and one had drowsiness.
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PMID:Clonidine effect on spasticity: a clinical trial. 334 19

We investigated the influence of four substances on the excitability of lumbar motoneurons. These substances, three of which coexist in the same bulbospinal descending pathways that end, for the most part, around motoneurons (MNS), are: 5-hydroxytryptamine (5-HT), substance P (SP) and thyrotropin-releasing hormone (TRH). We also studied the effects of clonidine, an alpha 2 noradrenergic (NA) agonist. This study was carried out in rats spinalized at T5 and treated three weeks earlier with 5-7 dihydroxytryptamine (5-7 DHT). Under these conditions, the following responses were observed: 5-HTP (5-HT precursor) intraperitoneally (I.P.), 5-HT intrathecally (I.T.), TRH (I.P. or I.T.) and substance P (I.T.) all elicited strong excitation of MNS as measured by integrated EMG of the hindlimb muscles; substance P reduced by almost half the response to 5-HTP given one hour and 24 hours later; TRH given acutely did not modify the response to 5-HTP, but given chronically for 21 days markedly increased the response to this substance. Clonidine by itself decreased the excitability of MNS and antagonized the excitatory effects of 5-HTP and TRH. In two separate pilot trials, cyproheptadine, a 5-HTP antagonist, decreased the manifestations of spasticity in a patient with a partial spinal lesion. It would appear that clonidine may have potential use in the management of spasticity.
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PMID:Action of 5-hydroxytryptamine, substance P, thyrotropin releasing hormone and clonidine on spinal neuron excitability. 754 99

Clonidine is being used increasingly for treatment of spasticity in patients with spinal cord injury. Though hypotension, dry mouth, and constipation are well-documented possible adverse effects, the possibility of clonidine-induced bradycardia is less well recognized and is rare. This report describes a patient who developed spasticity following a traumatic spinal cord injury. After clonidine was initiated, the patient's spasticity improved. However, he developed significant bradycardia. Once clonidine was discontinued, the resting heart rate returned to normal. This case illustrates an unusual adverse effect of clonidine. Possible mechanisms by which clonidine decreases spasticity are described, probable mechanisms of induced bradycardia are reviewed, and specific treatment recommendations for the use of clonidine in spinal cord injured patients are presented.
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PMID:Clonidine-induced bradycardia in patients with spinal cord injury. 823 63

Clonidine, a centrally acting alpha 2 receptor adrenergic agonist, has been successfully used as adjunctive therapy in patients with spinal cord injury with problematic spasticity not adequately controlled by recognized spasmolytic agents. A transdermal system providing approximately constant and continuous systemic delivery of clonidine has been recently introduced to enhance patient compliance. However, experience with transdermal clonidine in the management of spasticity is limited. Three cases are presented of patients with spasticity as the result of cervical spinal cord injury, inadequately managed by oral baclofen, in whom transdermal clonidine was administered. Significant improvement in spastic hypertonia was observed in all three cases. Transdermally delivered clonidine was well tolerated, with reported side effects limited to dryness of the mouth.
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PMID:Effect of transdermal clonidine on spinal spasticity. A case series. 851 78

Tizanidine, an imidazoline derivative with alpha 2-receptor-mediated central muscle relaxant activity, is in widespread clinical use for the treatment of spasticity. To evaluate its possible role in anesthesia we assessed the sedative and sympatholytic effects of orally administered tizanidine in a double-blind, placebo-controlled, randomized, cross-over study in six healthy male volunteers. Three different doses of tizanidine (4, 8, and 12 mg) were tested and compared to clonidine 150 micrograms. The sedative and sympatholytic effects of tizanidine 12 mg were comparable in magnitude to those of clonidine 150 micrograms, but the effects of clonidine were longer lasting. Similarly, the observed decreases in arterial blood pressure (diastolic, 13% and 19%; systolic, 10% and 8% for tizanidine and clonidine, respectively) and salivation were comparable in magnitude but of shorter duration after tizanidine 12 mg than after clonidine. Clonidine and tizanidine 12 mg had also similar effects on the secretion of growth hormone. Our results indicate that the effects of a single 12-mg oral dose of tizanidine resemble those of 150 micrograms oral clonidine, but are of shorter duration. Tizanidine may thus be a useful alternative to clonidine as an orally active, short-acting alpha 2-adrenoceptor agonist in the perioperative period.
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PMID:The sedative and sympatholytic effects of oral tizanidine in healthy volunteers. 861 3


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