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)

The effect of the selective 5-HT3 receptor antagonists ICS 205-930 and MDL 72222 on head shaking behavior induced by L-5-HTP and behavioral symptoms induced with 5-methoxy-N,N,-dimethyltryptamine (5-MeODMT) in rats was evaluated. Both drugs dose-dependently reduced L-5-HTP-induced head shaking but were at least 600 times less potent than pirenperone and ketanserin and at least 50 times less potent than methysergide. ICS 205-930 and MDL 72222 were more than 1000 times less potent than pirenperone or methysergide and 100 times less potent than ketanserin in blocking 5-MeODMT-induced forepaw treading and tremor. Since it appears that head shakes induced by L-5-HTP are mediated by 5-HT2 receptors, these data suggest that ICS 205-930 and MDL 72222 do not significantly interact with 5-HT2 receptors in the brain. Furthermore, the data suggest that ICS 205-930 and MDL 72222 lack appreciable antagonistic activity at the 5-HT receptor(s) mediating those behavioral effects induced by 5-MeODMT.
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PMID:Effect of the selective 5-HT3 receptor antagonists ICS 205-930 and MDL 72222 on 5-HTP-induced head shaking and behavioral symptoms induced by 5-methoxy-N,N,dimethyltryptamine in rats: comparison with some other 5-HT receptor antagonists. 311 4

The anti-tremor activity of talipexole (6-allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo[4,5-d]azepine dihydrochloride, B-HT 920 CL2, Domin), a non-ergot dopamine D2 receptor agonist which possesses alpha 2-adrenoceptor agonistic and 5-HT3 receptor antagonistic properties, was examined in monkeys with a unilateral lesion in the ventromedial tegmentum. Talipexole dose dependently suppressed the tremor and had ED50 values of 34 micrograms/kg s.c. and 84 micrograms/kg p.o. The anti-tremor effect of talipexole occurred at much lower doses than that of an ergot dopamine receptor agonist, bromocriptine (2-bromo-alpha-ergocryptine mesilate, ED50; 2.5 mg/kg s.c.), and talipexole acted synergistically in combination with L-DOPA (3,4-dihydroxyphenylalanine). In ventromedial tegmentum-lesioned monkeys, anti-tremor doses of talipexole did not cause emetic behavior, but had sedative effects. Conversely, monkeys given bromocriptine exhibited oral movement, salivation and vomiting when anti-tremor effects were observed, but not marked sedative behavior at any of the doses investigated. During repeated administration of talipexole (a daily dose of 50 micrograms/kg s.c. for 21 days), the extent and duration of the anti-tremor effect did not change, but those of the sedative effect decreased gradually. The anti-tremor effect of talipexole was significantly suppressed by sulpiride, but not by SCH 23390 (7-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-ol) or yohimbine, while the sedative effect was inhibited by sulpiride and yohimbine. The main metabolites of talipexole had no anti-tremor or sedative effects. These results indicate that talipexole exerts its anti-tremor activity via selective dopamine D2 receptor stimulation.
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PMID:Anti-tremor activity of talipexole produced by selective dopamine D2 receptor stimulation in cynomolgus monkeys with unilateral lesions in the ventromedial tegmentum. 904 91

The use of ondansetron, a selective serotonin 5-HT3 receptor antagonist, is well established in patients with nausea and vomiting associated with cancer chemotherapy, radiotherapy or anaesthesia and surgery. The wide distribution of 5-HT3 receptors in the body and the role of these receptors in disease have provided the rationale for investigation of ondansetron in novel applications. Preliminary data have shown ondansetron to have clinical benefit in patients with nausea and vomiting associated with drug overdosage or poisoning, anti-infective or antidepressant therapies, uraemia or neurological trauma, and in patients with pruritus. Patients with gastrointestinal motility disorders (e.g. carcinoid syndrome, irritable bowel syndrome, diarrhoea associated with cryptosporidiosis or diabetes, and chronic refractory diarrhoea) have also shown some improvement when treated with ondansetron, as have patients with certain pain or CNS-related disorders [e.g. alcohol (ethanol) dependence, opiate withdrawal, vertigo, cerebellar tremor and Parkinson's disease treatment-related psychosis]. In contrast to conventional antiemetics, ondansetron is generally well tolerated with a lower incidence of sedation and only isolated case reports of extrapyramidal reactions. Furthermore, unlike dopamine receptor-blocking neuroleptics, ondansetron does not appear to worsen the symptoms of Parkinson's disease. Thus, in addition to its established indications, preliminary results suggest that ondansetron may be beneficial in a number of novel applications. This drug may represent a treatment alternative in patients with refractory disease, or an effective treatment of conditions for which current therapies are either poorly tolerated or not available. Further investigation of ondansetron in a range of potential new applications appears to be warranted.
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PMID:Ondansetron. A review of its pharmacology and preliminary clinical findings in novel applications. 911 22

In order to elucidate possible male/female differences in emesis, the effects of various emetogenic drugs (cisplatin, copper sulfate, veratrine, nicotine, serotonin) and motion stimulus were compared between male and female Suncus murinus. Cisplatin (IP), nicotine (SC), veratrine (SC) and copper sulfate (PO) induced dose-dependent emesis in either sex, and there was no apparent difference in estimated ED50 values. However, male animals tended to be more susceptible to serotonin-induced emesis. The ID50 values for tropisetron, a 5-HT3 receptor antagonist, to block serotonin-induced emesis were also similar between male and female animals. However, tropisetron was less effective against cisplatin-induced emesis in females. Therefore, cisplatin may release more serotonin to induce emesis in females. Reciprocal shaking (horizontal oscillation 40 mm, frequency 0.5 to 2.0 Hz, duration 5 min) induced more frequent emesis in male animals, and the latency to the first vomit was shorter in males than in females. These results suggest that there is substantial sex-dependent difference in the emetic responses and male animals are in general more susceptible. These results are discussed in the light of similar studies in man.
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PMID:Male/female differences in drug-induced emesis and motion sickness in Suncus murinus. 925 99

This is a first report on the investigation of the antidepressant activity of MCI-225 (4-(2-fluorophenyl)-6-methyl-2-(1-piperazinyl)thieno[2,3-d]pyrimidine monohydrate hydrochloride, CAS 99487-26-0) in comparison with maprotiline (CAS 10347-81-6), desipramine (CAS 58-28-6), imipramine (CAS 113-52-0) and trazodone (CAS 25332-39-2). MCI-225 inhibited the synaptosomal uptake of noradrenaline (NA, Ki = 35.0 nmol/l), serotonin (5-HT, Ki = 491 nmol/l), and dopamine (Ki = 14,800 nmol/l), although it did not inhibit MAO-A and MAO-B activities. MCI-225 showed high affinity only for the 5-HT3 receptor (Ki = 81.0 nmol/l) among all receptors tested including M1, M2, alpha 1, and H1 receptors. The inhibition of the von Bezold-Jarisch reflex by MCI-225 (ID50 = 22.2 mg/kg, p.o.) suggests its antagonistic action on the 5-HT3 receptor. MCI-225 dose-dependently reduced reserpine-induced hypothermia (0.3-10 mg/kg, p.o.) and potentiated yohimbine-induced lethality (3-100 mg/kg, p.o.) in mice. These effects of MCI-225 were as potent as desipramine and more potent than maprotiline, imipramine and trazodone. MCI-225 and desipramine did not change either 5-HTP-induced head movements or p-CA-induced hyperactivity in rats. In forced swimming tests in rats, the minimum effective doses of MCI-225, maprotiline, desipramine, and imipramine were 1, 30, 10 and 30 mg/kg, p.o., respectively, for 5-days administration. Only MCI-225 had shown its full activity with this short term treatment. MCI-225 (10 mg/kg, p.o.) decreased the REM sleep period without affecting slow-wave sleep or wakefulness in rats. Even at 100 mg/kg, p.o. MCI-225 and trazodone did not inhibit oxotremorine-induced tremor, lacrimation or salivation in mice in contrast with imipramine. These results suggest that MCI-225, which selectively inhibits NA uptake and antagonizes the 5-HT3 receptor, has potential as a new type of potent antidepressant.
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PMID:Pharmacological profile of the novel antidepressant 4-(2-fluorophenyl)-6-methyl-2-(1-piperazinyl)thieno-[2,3-d]pyrimidine monohydrate hydrochloride. 945 Jan 61

Cerebellar tremor is a frequent and disabling symptom in multiple sclerosis (MS) patients. Supportive pharmacological treatment with different drugs showed only minor effects in a few studies and in clinical practice. Encouraged by previous studies with ondansetron, a 5HT3-antagonist, we conducted a small open-label, prospective and controlled study with 14 MS patients suffering predominantly from cerebellar tremor of the upper extremities. Principal outcome measure to evaluate a functional improvement of the single intravenous administered ondansetron injection was the subject performance in the 9-hole-peg-test (9HPT) and 3 blind assessed upper extremity writing and copying tasks. We neither found significant improvement in the upper extremity tests nor in the subjective response of the patients. In conclusion we could not confirm a beneficial effect of ondansetron on cerebellar tremor of MS patients.
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PMID:Failure of ondansetron in treating cerebellar tremor in MS patients--an open-label pilot study. 1169 26

Receptors of the Cys-loop family are central to neurotransmission and primary therapeutic targets. In order to decipher their gating and modulation mechanisms, structural data is essential. However, structural studies require large amounts of pure, functional receptors. Here, we present the expression and purification of the mouse serotonin 5-HT3 receptor to high purity and homogeneity levels. Inducible expression in human embryonic kidney 293 cells in suspension cultures with orbital shaking resulted in yields of 6-8mg receptor per liter of culture. Affinity purification using a strep tag provided pure protein in active form. Further deglycosylation and removal of the purification tag led to a pentameric receptor after size-exclusion chromatography, at the milligram scale. This material is suitable for crystallography, as demonstrated by X-ray diffraction of receptor crystals at low resolution.
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PMID:Large scale expression and purification of the mouse 5-HT3 receptor. 2374 84