Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Harmaline increases cerebellar 3':5'-cyclic guanosine monophosphate (cGMP) content in a dose-related manner; this increase is prevented by a pretreatment with 3-acetylpyridine (3-AP) (0.66 mmol/kg) which destroys climbing fibers and inhibits harmaline-induced tremor. The cerebellar cGMP content increases after isoniazid; this response remains unchanged in rats pretreated with 3-AP. Since isoniazid decreases cerebellar gamma-aminobuturic acid (GABA) levels, the increase in cGMP content might reflect a reduction in the availability of GABA at the level of postsynaptic receptors. Apomorphine (a dopamine receptor agonist) and haloperidol (a dopamine receptor blocker) increase or decrease the cGMP content of cerebellar cortex, respectively. Neither drug changes the guanylate cyclase activity of cerebellar homogenates; moreover their action on cerebellar cGMP content persists after 3-AP. Chloropromazine, like haloperidol, decreases the cerebellar cGMP content. The increase in cerebellar cGMP content elicited by apomorphine can be differentiated from that elicited by harmaline or isoniazid; presumably apomorphine indirectly activates mossy fibers. The decrease in cerebellar cGMP content elicited by haloperidol can be differentiated from that elicited by diazepam; perhaps haloperidol reduces the mossy fiber input to the cerebellum. We suggest that the cGMP content of cerebellar cortex fluctuates in response to changes in the afferent stimulatory input to the cerebellum; it increases when the activity of either climbing or mossy fibers is increased; it decreases when either of these two stimulatory inputs is reduced.
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PMID:Pharmacologically induced changes in the 3':5'-cyclic guanosine monophosphate content of rat cerebellar cortex: difference between apomorphine, haloperidol and harmaline. 1 99

Rats were made dependent on morphine by implantation of a pellet and withdrawal was precipitated by the injection of naloxone 72 hours later. Withdrawal was assessed by scoring each of the following signs individually: chewing, licking, teeth chattering, facial tremor, grooming, writhing, diarrhea, weight loss, wet dog shakes, head shakes and hypothermia. The role of dopamine in withdrawal was determined by pretreating the animals with apomorphine or pimozide. Apomorphine in the lower dose range (0.625-1.25 mg/kg) produced a significant decrease in teeth chattering, writhing, weight loss and wet dog shakes. The high dose of apomorphine (2.5 mg/kg) significantly inhibited all features of the withdrawal except writhing and weight loss. Pimozide caused a significant increase in chewing, writhing and head shakes, but only with the highest dose used (0.5 mg/kg). Pimozide (0.5 mg/kg) significantly reduced withdrawal hypothermia, but apomorphine had no effect on this sign except at the highest dose when withdrawal hypothermia was increased.
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PMID:Dopaminergic mechanisms in precipitated withdrawal in morphine-dependent rats. 55 7

Seventeen patients with either Parkinson's disease or post-encephalitic parkinsonism were treated with Piribedil, an apomorphine-like drug, in single blind conditions for a period ranging from five weeks to twenty-four months. The analysis of the results shows that Piribedil modifies the extrapiramidal symptomatology being specially effective against the tremor either when used alone or in association with L-Dopa. The side effects noticed during treatment with Piribedil are similar to those of Apomorphine, and are dose-dependent.
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PMID:[Piribedil in the treatment of Parkinson disease (author's transl)]. 77 98

The recording technique described makes possible the detailed analysis of hypertonia and tremor in Parkinson's disease, as well as the action of different drugs. It may contribute to the understanding of the physiopathological basis of these motor disturbances and the mode of action of anti-parkinsonian drugs. It also represents a reliable method of repeated observation, independent of subjective factors, in the evaluation of the long-term effectiveness of a medication. We were particularly concerned with the evaluation and comparison of the effect of different drugs in the course of a short study, involving the administration of a single dose of the medications used. In this way were studied: Apomorphine, given sub-cutaneously in non-emetic doses, which decreases in a constant and spectacular fashion both tremor and hypertonia ; Piribedil (1-3 mg IV) ; L-Dopa (100 mg IV) ; Ro-080576/007 F in a dose of one capsule containing 200 mg of L-Dopa and 50 mg of L-dopa-decarboxylase inhibitor. The effect of these various medications was invariable greater than that of a placebo and lasted much longer. With these doses, and under the special experimental conditions of this study, Piribedil was better tolerated and in general more active than L-dopa, in particular in relation to tremor. The action observed in the course of this short study prior to treatment might, to a certain extent, make it possible to predict the effect of long-term treatment.
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PMID:[Polygraphic recording of tremor and of hypertonic phenomena. Application to the action of various drugs]. 110 46

We studied the biochemical and pharmacologic modes of action of piribedil and apomorphine in the rat. Although both drugs have many points in common, they are also different in many of their manifestations. Apomorphine causes high-intensity, short-duration stereotyped behavior; it is distributed within the brain in uneven fashion, the striatum being the area of lowest concentration as measured by fluorometry. Direct stereotactic injection within the dopaminergic mesolimbic system, and particularly the tuberculum olfactorium, produced constant intense responses. All effects of apomorphine can be blocked by pimozide, but propanolol, a beta blocker, only reduces aggression and ferocity, leaving stereotyped behaviors intact. Finally, L-5-HTP tends to reduce aggression, ferocity, and to a lesser extent stereotypy; MIF or piribedil, as well as reserpine, potentiates the stereotyped behaviors induced by apomorphine, whereas L-DOPA usually decreases them. Piribedil, on the other hand, causes low-intensity, long-duration stereotyped behavior. It is distributed within the brain almost uniformly. Most effects of piribedil can be blocked by pimozide, but propanolol blocks only aggression and ferocity, leaving stereotyped behaviors intact. On the other hand, clonidine, an alpha-receptor agonist, blocks stereotyped behaviors induced by piribedil but markedly increases aggression, ferocity, and motor activity. L-5-HTP and L-DOPA have little effect on piribedil-induced manifestations. Reserpine decreases piribedil stereotypy. The main metabolite of piribedil, S 584, had no clear-cut pharmacologic action in our hands at the dosage used. It is concluded that both apomorphine and piribedil produce stereotyped behavior by modifying the physiologic balance between mesolimbic and nigrostriatal dopaminergic systems. The other actions of apomorphine and piribedil upon aggression, ferocity, and motor activity are not always in parallel and depend probably on the fact that piribedil is less specific, affecting also noradrenergic, serotonergic, histaminergic, and/or cholinergic circuits. The usefulness of piribedil against some forms of human tremor and its low-intensity antiakinetic action probably result from this pattern of pharmacologic activity.
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PMID:Apomorphine and piribedil in rats: biochemical and pharmacologic studies. 117 Jul 16

Noradrenaline (NA), methoxamine, dopamine (DA), given intracerebroventricularly (ICV), and L-DOPA, administered systemically, significantly blocked wet dog shakes (WDS) produced by carbachol chloride (10 microgram/10 microliter, ICV) in rats. Reserpine, alpha-methyl-p-tyrosine and FLA 63 did not affect WDS, while diethyldithiocarbamic acid depressed it. Aceperone and yohimbine weakened shaking response to carbachol but phentolamine given ICV showed no effect on WDS. Propranolol and isoproterenol administered ICV did not significantly influence WDS. Apomorphine failed to affect WDS induced by carbachol. Pimozide and spiperone were also ineffective against WDS, but amphetamine and metoclopramide efficiently blocked it. Selective depletion of brain NA concentration considerably enhanced WDS, while selective depletion of brain DA concentration failed to affect it. These results suggest that carbachol-induced WDS behavior is under the inhibitory control of noradrenergic neurons.
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PMID:The involvement of catecholaminergic mechanisms in the appearance of wet dog shakes produced by carbachol chloride in rats. 628 Jun 27

An acute administration of various doses of apomorphine, a dopaminergic agonist, and of dopaminergic receptor blockers (domperidone, sulpiride, haloperidol), was double-blindly achieved in a parkinsonian patient also suffering from dyskinesia. Apomorphine improved tremor and dyskinesia proportionnally to the dose. Domperidone did not prevent from this beneficial effect whereas sulpiride or haloperidol revealed a competitive antagonism versus apomorphine.
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PMID:[Modification of extrapyramidal signs by apomorphine associated with various dopaminergic antagonists]. 714 25

Rats were injected unilaterally into the rostral substantia nigra pars compacta with 8 micron of 6-OHDA. Those animals that conformed to be behavioral criteria for an effective nigrostriatal dopamine lesion by turning ipsilaterally to the injected side upon IP amphetamine, and contralaterally upon apomorphine injection were bilaterally detelencephalized (neocrotex, hippocampus, striatum, septum, amygdaloid complex were removed). Most detelencephalized animals exhibited spontaneous turning to the contralateral side, i.e. no longer behaved like 6-OHDA-lesioned rats, but instead, acted like animals with nigral kainic acid or electrolytic lesions. Amphetamine (2-3 mg/kg) increased general activity but no longer influenced turning. Apomorphine in doses of 2-3 mg/kg completely suppressed all motility. In small doses (0.1-0.2 mg/kg) it reversed the spontaneous contraversive turning. This effect could be blocked by haloperidol (0.1 mg/kg) pretreatment. High doses of haloperidol (5.0-7.5 mg/kg) reversed the direction of circling from contraversive to ipsiversive. Arecoline (10-12 mg/kg) induced tremor as in normal animals. Atropine (50-100 mg/kg) did not affect turning, but increased activity level in the thalamic rats.
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PMID:The influence of unilateral 6-OH-dopamine lesions of the substantia nigra in the absence of the telencephalon. 747 Sep 60

The aim of the present work was to study the behavioral effects elicited in adult cats by the selective D1 agonist, SKF 38393, and the D2 agonist, LY 171555, comparing their effects with those evoked by apomorphine. In 10 adult cats, 0.5, 1.0, 4.0, and 8.0 mg/kg IP of SKF 38393 were administered at random. A dose-response effect was observed related to alertness, indifference, and locomotion. The overall effect of SKF 38393 was inhibitory. To the same 10 animals, LY 171555 in doses of 0.25, 0.5, and 1.0 mg/kg were injected IP. This drug had an excitatory and more complex effect than what was observed with the D1 agonist. Increases in locomotion, in alertness, indifference, fear, olfaction, pupillary dilation, hallucination, limb flicking, and head shaking were recorded. Apomorphine given to the same cats, in a dose equimolar to 1.0 mg/kg of LY 171555, elicited behaviors that resembled those elicited by the latter drug, but of a lesser intensity and duration. The interval between the different treatments was approximately 2 months. These results show clearly that the D2 receptor is the main dopaminergic receptor involved in the mechanism of production of most of the behavioral effects produced by some of the dopaminergic agonist drugs like apomorphine.
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PMID:Behavioral effects evoked by SKF 38393 and LY 171555 in adult cats. 761 Jan 53

We present a review of the recent literature and personal experience with apomorphine in patients with Parkinson's disease. Apomorphine is a potent D1 and D2 dopaminergic agonist. It has a rapid and short duration effect after subcutaneous administration at doses ranging from 15 to 180 micrograms/kg. Plasma maximal concentration is reached in 8-16 minutes, with a plasma half life of 34-70 minutes. Bioavailability is close to 100%. Repeated injections in patients show post-stimulative hyposensitivity. Apomorphine test appears very useful for the differential diagnosis between idiopathic Parkinson's disease and other Parkinson plus syndromes, and as a predictive test for dopaminergic responsiveness. Appropriate doses are able to alleviate akinesia, rigidity and tremor. Recent therapeutic trials have demonstrated the high interest of intermittent multiple subcutaneous apomorphine injections to cut the "off" motor phases in fluctuating parkinsonian patients under chronic levodopa treatment. In some cases, continuous apomorphine subcutaneous infusion with a portable pump may be required, particularly when levodopa treatment is temporarily interrupted, as after abdominal surgery. During long-term treatment, the apomorphine dose able to relieve akinesia remains stable. Peripheral side effects such as nausea and hypotension may be prevented by the co-administration of domperidone, a peripheral dopaminergic antagonist. Cutaneous fibrous nodules and psychiatric symptoms may occur, but usually at high dosages with continuous infusion. Local allergic effects have limited the use of other routes of administration, such as intranasal, sublingual, and rectal routes. Apomorphine is also used as a pharmacological tool for clinical research with the aim of a better understanding of the pathophysiology of Parkinson's disease.
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PMID:Apomorphine in patients with Parkinson's disease. 766 39


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