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

Baboons received continuous intragastric infusions of diazepam (20 mg/kg per day) for one or more months. While diazepam treatment continued, baboons received intragastric doses of Ro 15-1788 (0.032-32.0 mg/kg) or CGS 8216 (1.0-100.0 mg/kg) at intervals of two or more weeks. Baboons were observed following administration of these antagonists for the presence of precipitated withdrawal signs. The following results were obtained: (1) both Ro 15-1788 and CGS 8216 produced signs of precipitated withdrawal in the baboon; (2) a more severe overall withdrawal syndrome was precipitated with Ro 15-1788 than with CGS 8216 at testable doses; (3) Ro 15-1788 produced dose-related increases in the overall severity of withdrawal, while CGS 8216 did not produce a clear dose-related increase in the overall severity of withdrawal; (4) dose-effect curves for Ro 15-1788 for certain signs (e.g. limb-tremor) were monotonicly increasing, while for other signs dose-effect curves plateaued at lower doses of Ro 15-1788 (e.g. retching and vomiting) or were an inverted U-shape (e.g. scratching). CGS 8216 precipitated withdrawal signs were less clearly dose-dependent; (5) onset of Ro 15-1788 precipitated withdrawal signs were rapid (5-15 min) and reliable, while the onset of CGS 8216 precipitated withdrawal signs were generally slower (approximately 30 min) and more variable; (6) at doses of Ro 15-1788 and CGS 8216 that produced equal levels of vomiting and retching, Ro 15-1788 produced more limb-tremor than CGS 8216. These studies indicate that Ro 15-1788 and CGS 8216 may produce quantitatively and qualitatively different precipitated withdrawal syndromes.
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PMID:Effects of Ro 15-1788 and CGS 8216 in diazepam-dependent baboons. 312 66

Baboons implanted with intragastric catheters were given diazepam (10 milligrams per kilogram of body weight) twice daily for 45 consecutive days. On days 7 and 35, they were given intramuscular injections of the benzodiazepine receptor antagonist Ro 15-1788. Mild and intermediate withdrawal signs, including retching and vomiting, were observed after 7 days of diazepam, and more frequent and intense withdrawal signs, including tremor and convulsion, occurred after 35 days of diazepam. With the termination of the diazepam injections after 45 days, a mild to intermediate withdrawal syndrome was observed over the next 15-day period.
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PMID:Precipitated withdrawal by a benzodiazepine receptor antagonist (Ro 15-1788) after 7 days of diazepam. 628 79

The drug UM 1046 (N-cyclopropylmethyl-1,2,3,4,5,6-hexahydro-8-hydroxy-6-methyl-3-benzazoc ine), administered to opiate-naive monkeys, produces certain behavioral responses resembling antagonist-precipitated morphine withdrawal (Swain and Seevers, 1975). In the present study, UM 1046 (5.6 mg/kg, i.v.), administered to naive rats, produced a syndrome that consisted primarily of retching, chewing, teeth chattering, shaking and abnormal postures. It was of interest to determine whether UM 1046 had an effect on noradrenergic neurons of the locus coeruleus (NE-LC) since increased activity of these cells has been reported to occur during antagonist-precipitated opiate withdrawal (Aghajanian, 1978) and after the administration of drugs that mimic this syndrome in normal animals. (i.e. methylxanthine phosphodiesterase inhibitors, Grant and Redmond, 1981). In the present study, UM 1046 (1.0-5.6 mg/kg, i.v.) caused a dose-dependent increase (of up to 200%) in the spontaneous discharge rate of noradrenergic neurons of the locus coeruleus in rats anesthetized with halothane. The time-course of this effect was similar to the time-course of the behavioral syndrome described above. Stimulation of central muscarinic receptors is integrally involved in the response to this drug since the effects of UM 1046 (5.6 mg/kg) were antagonized by scopolamine (0.5 mg/kg, i.v.), but not by methylscopolamine (1.0 mg/kg, i.v.). Unlike systemic administration, iontophoretic application of UM 1046 did not consistently increase the spontaneous discharge rate of these cells, indicating that the site of action of the drug may be outside the nucleus locus coeruleus. This study complements previous findings of increased activity in noradrenergic neurons of the locus coeruleus during withdrawal-like behavior. In addition, the results are compatible with others which suggest that a cholinergic link is essential for the withdrawal-like actions of the benzazocine.
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PMID:Activation of locus coeruleus neurons in the rat by a benzazocine derivative (UM 1046) that mimics opiate withdrawal. 668 52

alpha-Naphthoxyacetic acid (alpha-NOAA), one of the retching-inducers, elicited a dose-dependent jumping behavior shortly after i.p. administration in doses ranging from 250 to 700 mg/kg in ddY mice, the incidence of jumping being 97% at a dose of 700 mg/kg. alpha-NOAA also induced hypothermia, retching, head shaking, salivation and lacrimation. Phentolamine, reserpine, disulfiram, tranylcypromine, haloperidol, scopolamine, bicuculline, diazepam and lithium among the drugs tested inhibited to a certain degree but not markedly the alpha-NOAA-induced jumping behavior. However, the behavior was markedly inhibited by a dopaminergic agonist, apomorphine (1 mg/kg, i.p.), and this inhibitory effect was significantly antagonized by a dopaminergic antagonist, haloperidol (2 mg/kg, i.p.). These findings suggest that the jumping behavior elicited by alpha-NOAA may be due to the inhibition of dopaminergic neuron activity.
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PMID:Dopaminergic inhibition involved in the alpha-naphthoxyacetic acid-induced jumping behavior in mice. 738 15

The D2 dopamine agonist piribedil is not widely used in the treatment of Parkinson's disease because it was thought to be effective mainly on parkinsonian tremor and to produce a high incidence of peripheral side effects, particular nausea. In this study, we used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated primates to reevaluate the antiparkinsonian ability of piribedil after its oral administration in the presence or absence of domperidone pretreatment. Adult common marmosets (Callithrix jacchus) were treated with the nigral toxin MPTP to induce a parkinsonian syndrome characterised primarily by bradykinesia and other motor deficits. Oral administration of a solution of piribedil [1-(3,4-methylenedioxybenzyl)-4-(2-pyrimidinyl)piperazine] produced a dose-related reversal of all MPTP locomotor and behavioural deficits. However, this effect was short lived and associated with unwanted effects, particular nausea and retching, which clearly hindered locomotion. In contrast, after pretreatment with the peripheral dopamine antagonist domperidone, administration of piribedil did not induce nausea or retching in MPTP-treated marmosets. In these animals, piribedil caused a more marked and longer lasting enhancement of locomotor activity and a further reduction in behavioural deficits than that observed after administration of piribedil alone. In addition, piribedil induced increased vigilance and awareness. These data show that piribedil can reverse akinesia and rigidity in MPTP-treated primates. In addition, they show the drug to be effective without peripheral side effects when used in conjunction with domperidone. These data indicate that piribedil should be an effective monotherapy for Parkinson's disease.
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PMID:An appraisal of the antiparkinsonian activity of piribedil in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated common marmosets. 868 81

The characteristics of recovery from total intravenous anesthesia (TIVA) with propofol and inhalation anesthesia with isoflurane was clinically compared in 149 client-owned dogs that anesthetized for surgical or diagnostic procedures. In all dogs, anesthesia was induced with an intravenous injection of propofol following premedication with acepromazine or diazepam. As a result, 58 dogs anesthetized with propofol-TIVA showed slower but smoother recovery than 91 dogs anesthetized with isoflurane anesthesia. The dogs stood at 34.5 +/- 19.3 and 27.7 +/- 17.2 min after propofol-TIVA and isoflurane anesthesia, respectively. Adverse effects, including hypersalivation, neurologic excitement (paddling, muscle tremor/twitching, opisthotonos) and vomiting/retching, were observed in similar infrequent incidences during the recovery from both anesthetic protocols. Propofol-TIVA is suggested to be an alternative anesthetic protocol for canine practice.
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PMID:Clinical comparison of recovery from total intravenous anesthesia with propofol and inhalation anesthesia with isoflurane in dogs. 1805 35