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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Behavioral effects induced by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; i.e., lower lip retraction, flat body posture, and forepaw treading) were examined in rats during ethanol withdrawal following a 2-week period of access to a liquid diet containing 9% (v/v) ethanol. After an 18 h withdrawal period, tolerance to 8-OH-DPAT-induced flat body posture and, conversely, sensitization to the effects of 8-OH-DPAT on lower lip retraction were observed in the 9% ethanol group as compared to control rats fed an isocaloric diet. In contrast, 8-OH-DPAT-induced forepaw treading in the 9% ethanol group was not significantly different in comparison to control rats. Plasma corticosterone levels were significantly higher in the ethanol-exposed group than in control animals, an effect which was not additive with the increase in corticosterone levels normally observed after the administration of low doses of 8-OH-DPAT. Altered flat body posture and lower lip retraction responses to a submaximal dose of 8-OH-DPAT (2.5 mg/kg i.p.) were still observed as late as 3 days after withdrawal of the 9% ethanol liquid diet, but were no longer apparent at 7 days. Interestingly, prominent ethanol withdrawal signs such as tremor and rigidity, while occurring on the first day, were completely absent on the third day. Taken together, these results indicate that chronic ethanol exposure differentially alters sensitivity to several pharmacological effects of the 5-HT1A receptor ligand 8-OH-DPAT. They further support the involvement of 5-HT (5-hydroxytryptamine, serotonin) systems in alcohol abuse and therapeutic interventions using 5-HT1A ligands.
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PMID:Modification of behavioral effects of 8-hydroxy-2-(di-n-propylamino)tetralin following chronic ethanol consumption in the rat: evidence for the involvement of 5-HT1A receptors in ethanol dependence. 852 4

MF-268 bitartrate [(3a S, 8a R)-1,2,3,3a,8,8a-hexahydro-1,3a,8-trimethylpyrrolo[2,3-b]indol- 5-ol[8-(cis2,-6-dimethyl-morpholin-4-yl)octyl]-carbamate L-bitartrate hydrate; Mediolanum Farmaceutici, Milan, Italy] is a pseudo-reversible carbamate-type cholinesterase inhibitor (ChEI) which interacts with the catalytic and regulatory anionic site of the enzyme. Its effects on extracellular levels of acetylcholine (ACh), norepinephrine (NE), dopamine (DA), and serotonin (5-HT, 5-hydroxytryptamine) were studied in rat cortex by using a microdialysis technique coupled with high-performance liquid chromatography-electrochemical detection (HPLC-ECD). Conscious, freely moving rats were systemically [per os (p.o.) and subcutaneously (s.c.)] administered MF-268 with no ChEI in the probe. Cholinesterase inhibition in brain was assayed in parallel experiments. Oral administration of MF-268 (0.5, 2.0, and 5.0 mg/kg) produced a significant increase of extracellular ACh in cortex; the maximal increase was 300% [not significant (n.s.)], 460% and 1,200%, respectively. Maximal cholinesterase (ChE) inhibition was 2.3% (n.s.) at 9 hr and 9.7% (P < .05) at 12 hr after the 2.0 and 5.0 mg/kg doses, respectively. Norepinephrine and DA levels were increased 180% and 100% after the 5.0 mg/kg dose, respectively; 100% and 60% after the 2.0 mg/kg dose, respectively; and 70% for both amines after the 0.5 mg/kg dose, respectively. The elevation lasted at least 5 hr with the 2.0 and 5.0 mg/kg doses. There were no major changes in 5-HT levels at these three doses. Subcutaneous administration (0.5 and 2.0 mg/kg) produced a maximal 360% (5.5 hr) and 2,500% (5 hr) increase in extracellular ACh, respectively. Maximal ChE inhibition was 13% (0.5 mg/kg) and 41% (2.0 mg/kg). Neither 0.5 nor 2.0 mg/kg produced a consistent modification of NE. Only a transient increase in DA was seen with the 0.5 mg/kg dose. There were no changes in 5-HT levels at these two doses. MF-268-treated animals showed slight cholinergic side effects (chewing, tremor) at both doses. MF-268 administered intracortically through the microdialysis probe at a concentration of 50 microM induced a 5,900% increase in ACh levels at 6 hr. This effect started 30 min after injection and continued throughout the period of administration. MF-268 produced a significant decrease in NE levels (-44%) starting at 30 min, and a slight but significant increase in DA levels of 45% at 2.5 hr. A significant increase of 5-HT (58%) was also observed starting at 4 hr. Slight symptoms of cholinergic toxicity were observed during intracortical administration.
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PMID:Effects of MF-268, a new cholinesterase inhibitor, on acetylcholine and biogenic amines in rat cortex. 883 83

Ethanol is metabolized in the brain by catalase/H2O2 to yield acetaldehyde and by an ethanol-inducible form of cytochrome P450 (P450 IIE1) in a reaction that yields oxygen radicals. Within the cytoplasm of serotonergic axon terminals these metabolic pathways together provide conditions for the endogenous synthesis of 1-methyl-6-hydroxy-1,2,3,4-tetrahydro-beta-carboline (1), by reaction of acetaldehyde with unbound 5-hydroxytryptamine (5-HT), and for the oxygen radical-mediated oxidation of this alkaloid. The major initial product of the hydroxyl radical (HO.)-mediated oxidation of 1 in the presence of free glutathione (GSH), a constituent of nerve terminals and axons, is 8-S-glutathionyl-1-methyl-1,2,3,4-tetrahydro-beta-carboline-5,6-dione (6). When administered into the brains of mice, 6 is a potent toxin (LD50 = 2.9 microg) and evokes episodes of hyperactivity and tremor. Compound 6 binds at the GABA(B) receptor and evokes elevated release and turnover of several neurotransmitters. Furthermore, the GABA(B) receptor antagonist phaclofen attenuates the behavioral response caused by intracerebral administration of 6. These observations suggest that 6 might be an inverse agonist at the GABA(B) receptor site. Accordingly, it is speculated that ethanol drinking might potentiate formation of 6 that contributes to elevated release of several neurotransmitters including dopamine (DA) and endogenous opioids in regions of the brain innervated by serotonergic axon terminals. Subsequent interactions of DA and opioids with their receptors might be related to the initial development of dependence on ethanol. Redox cycling of 6 (and of several putative secondary metabolites) in the presence of intraneuronal antioxidants and molecular oxygen to produce elevated fluxes of cytotoxic reduced oxygen species might contribute to the degeneration of serotonergic pathways. Low levels of 5-HT in certain brain regions of the rat predisposes these animals to drink or augments drinking. Accordingly, 6, formed as a result of ethanol metabolism in the cytoplasm of certain serotonergic axon terminals, might contribute to the initial development of dependence on ethanol, by mediating DA and opioid release, and long-term preference and addiction to the fluid as a result of the progressive degeneration of these neurons.
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PMID:Putative oxidative metabolites of 1-methyl-6-hydroxy-1,2,3,4-tetrahydro-beta-carboline of potential relevance to the addictive and neurodegenerative consequences of ethanol abuse. 916 Jul 98

The serotonin syndrome is the result of excess stimulation of central nervous 5-hydroxytryptamine (5HT)-1a and 5HT-2 receptors. The diagnosis requires a history of exposure to agents active at serotonin receptors and the presence of alterations in mental status, autonomic instability, and neuromuscular abnormalities such as tremor, hyperreflexia, or myoclonus. In this descriptive case series, five cases of serotonin syndrome are reported. All patients gave a history of recent exposure to one or more serotonergic medications, including moclobemide, paroxetine, sertraline, and venlafaxine, with clinical evidence of serotonin syndrome. All patients were administered cyproheptadine (4-8 mg orally) for serotonergic signs. Three had complete resolution of signs within 2 h of administration. Another two had a residual tremor or hyperreflexia following the first dose, which resolved following a repeat dose. There were no adverse outcomes from cyproheptadine use. The role of specific serotonin receptor antagonists such as cyproheptadine in the treatment of the serotonin syndrome remains to be delineated. Its use should be considered an adjunct to supportive care. Currently, it is unknown whether cyproheptadine modifies patient outcome.
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PMID:Treatment of the serotonin syndrome with cyproheptadine. 2714 91

The aim of this study was to investigate the neurotransmissions involved in the antinociceptive effect of tramadol in the formalin test, which is an animal model of acute and tonic pain. A subcutaneous injection of formalin produces a biphasic nociceptive response: phase 1 (0-10 min-acute pain) and phase 2 (21-60 min-tonic pain). Nociceptive activity is reduced greatly during the 10 min between these two phases. We measured in mice the effects of (+/-)-tramadol, and of (+)- and (-)-tramadol administered before the induction of pain by formalin, in the presence and absence of drugs that act on the opioidergic, serotonergic and noradrenergic systems (naloxone, ketanserin, fluoxetine, maprotiline). With respect to animals treated with formalin alone, (+/-)-tramadol and its enantiomers significantly reduced the duration of nociceptive behaviours (lifting, licking, favouring, shaking, and flinching of the formalin-treated paw) during phase 2. This effect was prevented by the 5-HT(2) receptor antagonist ketanserin, but not by naloxone which, on the contrary, was able to prevent the antinociceptive effect of morphine. Naloxone and ketanserin did not affect the duration of nociceptive behaviour in animals not treated with tramadol. Fluoxetine (a selective 5-hydroxytryptamine (5-HT) reuptake inhibitor), but not maprotiline (a selective norepinephrine reuptake inhibitor), potentiated the antinociceptive effect of (+/-)-tramadol. In conclusion, we demonstrate that the serotonergic pathway is responsible for the antinociceptive effect of tramadol in phase 2 of the formalin test, and that this effect is mediated by 5-HT(2) receptors.
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PMID:The antinociceptive effect of tramadol in the formalin test is mediated by the serotonergic component. 1207 82

The administration of tremogenidine doses of Tremorine, 1,4-dipyrrolidino-2 butyne, is followed by a significant decrease in the concentration of norepinephrine in the brain stem of three common laboratory species. The change in the concentration proceeds at a rate which coincides with the occurrence of the tremor in each of these species. In the rat, the change in norepinephrine is followed by a progressive increase in the concentration of 5-hydroxytryptamine in the brain stem. Bilateral adrenalectomy in the rat enhances the Tremorine-induced changes in the concentration of norepinephrine and antagonizes the increase in the concentration of S-hydroxytryptamine.
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PMID:TREMORINE: ITS EFFECT ON AMINES OF THE CENTRAL NERVOUS SYSTEM. 1404 64

5-hydroxytryptamine (5-HT) syndrome is a dangerous condition of 5-HT excess that can occur in the case of co-administration of a monoamine oxidase (MAO) inhibitor and a serotonin reuptake inhibitor (SSRI). The goal of the present study was to investigate the effects of acute administration of MAO inhibitors and subchronic administration of fluvoxamine on 5-HT-related behaviors (head shaking and 5-HT syndrome) in rats treated with 5-hydroxytryptophan (5-HTP). Administration of the non-selective MAO inhibitor, pargyline, and the selective MAO-A inhibitor, clorgyline, resulted in 5-HT syndrome in 5-HTP-treated rats, and subchronic co-administration of fluvoxamine intensified the syndrome. However, administration of the selective MAO-B inhibitor, selegiline, did not induce 5-HT syndrome with or without subchronic fluvoxamine co-administration. These data suggest that non-selective MAO and selective MAO-A inhibitors can induce 5-HT syndrome in humans when co-administered with SSRI. Further, the risk of 5-HT syndrome may be lower with the selective MAO-B inhibitor, selegiline.
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PMID:Effects of co-administration of a selective serotonin reuptake inhibitor and monoamine oxidase inhibitors on 5-HT-related behavior in rats. 1648 9

Serotonin syndrome is a potentially life-threatening adverse drug reaction caused by excessive serotonergic agonism in central and peripheral nervous system serotonergic receptors (Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med 2005;352:1112-1120). Symptoms are characterized by a triad of neuron-excitatory features, which include (a) neuromuscular hyperactivity -- tremor, clonus, myoclonus, hyperreflexia and, in advanced stages, pyramidal rigidity; (b) autonomic hyperactivity -- diaphoresis, fever, tachycardia and tachypnea; (c) altered mental status -- agitation, excitement and, in advanced stages, confusion (Gillman PK. Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity. Br J Anaesth 2005;95:434-441). It arises when pharmacological agents increase serotonin neurotransmission at postsynaptic 5-hydroxytryptamine 1A and 5-hydroxytryptamine 2A receptors through increased serotonin synthesis, decreased serotonin metabolism, increased serotonin release, inhibition of serotonin reuptake or direct agonism of the serotonin receptors (Houlihan D. Serotonin syndrome resulting from coadministration of tramodol, venlafaxine, and mirtazapine. Ann Pharmacother 2004;38:411-413). The etiology is often the result of therapeutic drug use, intentional overdosing of serotonergic agents or complex interactions between drugs that directly or indirectly modulate the serotonin system (Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med 2005;352:1112-1120). Due to the increasing availability of agents with serotonergic activity, physicians need to more aware of serotonin syndrome. The following case highlights the complex nature in which serotonin syndrome can arise, as well as the proper recognition and treatment of a potentially life-threatening yet easily avoidable condition.
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PMID:Serotonin syndrome: a complex but easily avoidable condition. 1843 63

Patients are at high risk of developing serotonin-toxicity syndrome (toxidrome) when they take multiple serotonergic drugs, particularly co-administered with monoamine oxidase inhibitors or 5-hydroxytryptamine (5-HT) reuptake blockers. The toxidrome can vary from mild to severe. The primary goal of the present study was to understand the relationship between behavioral signs and degrees of toxidrome induced by 5-hydroxy-l-tryptophan (5-HTP) in clorgylinized rats. The severity was obtained by scoring behavioral signs including head shakes, penile erection, forepaw treading, hind limb abduction, Straub tail and tremor. It was found that 5-HTP produced a dose-dependent increase in degrees of the toxidrome. Furthermore, correlation between the toxidrome and changes in body-core temperature (delta Tcor) was determined. There was hypothermia in the mild toxidrome (delta Tcor<-1 degrees C), high hyperthermia in the severe toxidrome (delta Tcor>+2 degrees C) and a small change in T(cor) in the moderate toxidrome (-1 degrees C<delta Tcor<+2 degrees C). Thus, delta Tcor in response to drugs can be used to estimate the severity of the toxidrome. The second attempt was to identify the receptors mediating those changes. 5-HT1A receptors were involved in the hypothermic response while 5-HT2A and NMDA receptors mediated head shakes, hyperthermia, forepaw treading and Straub tail. Lastly, antidotal effect of cyproheptadine and (+)-MK-801 was examined. Both drugs blocked hyperthermia and death. However, the effects on mortality became poor when the antidotes were injected 60 min after high hyperthermia had been induced. These findings demonstrate the importance of the time frame using antidotes in the treatment of the 5-HT toxidrome.
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PMID:Characterization of serotonin-toxicity syndrome (toxidrome) elicited by 5-hydroxy-l-tryptophan in clorgyline-pretreated rats. 1849 1

A potent 5-hydroxytryptamine (5-HT)2A receptor inverse agonist and antagonist, ACP-103 [N-(4-fluorophenylmethyl)-N-(1-methylpiperidin-4-yl)-N'-(4-(2-methylpropyloxy)phenylmethyl) carbamide (2R,3R)-dihydroxybutanedioate (2:1, active:salt)], was evaluated for its ability to reduce the primary motor symptom of tremor using tacrine-induced tremulous jaw movements in rats, which is an animal model of parkinsonian tremor. Furthermore, ACP-103 was evaluated for its ability to reduce levodopa-induced dyskinesias in monkeys rendered parkinsonian with MPTP [1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine]. ACP-103 reduced tacrine-induced tremulous jaw movements in rats. In addition, ACP-103 administered in combination with levodopa caused a dose-related reduction in dyskinesias in monkeys. These data suggest that ACP-103 may have the potential to reduce tremor and levodopa-induced dyskinesias in Parkinson's disease.
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PMID:A 5-HT2A receptor inverse agonist, ACP-103, reduces tremor in a rat model and levodopa-induced dyskinesias in a monkey model. 1853 70


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