Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P46098 (5-HT3 receptor)
 2,290 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

(+)SKF 10,047 preferentially increased dopamine release in the nucleus accumbens compared to the striatum. Dopamine output was evaluated in the same freely moving rats by trans-cerebral dialysis. Clozapine and DAU 6215, a 5HT3 antagonist, which itself did not modify dopamine release in both areas, selectively antagonized (+)SKF 10,047-induced dopamine release in the nucleus accumbens. Haloperidol by itself increased dopamine release in both areas and these effects were additive with those induced by (+)SKF 10,047.
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PMID:Effect of haloperidol and clozapine on (+)SKF 10,047-induced dopamine release: role of 5-HT3 receptors. 149 54

Zacopride administered orally was more emetic in fed than in fasted ferrets. The emetic activity of zacopride (0.1 mg/kg p.o.) was inhibited (100%) by 0.1 mg/kg i.p. of zacopride and 1 mg/kg i.p. of ICS 205-930. Haloperidol (3.16 mg/kg i.p.) and prochlorperazine (3.16 mg/kg i.p.) were weakly effective. N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan amide, a 5-HT1P antagonist, was inactive. Thus, the emetic activity of zacopride, like that of cisplatin, is blocked by 5-HT3 receptor antagonists.
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PMID:Emetic activity of zacopride in ferrets and its antagonism by pharmacological agents. 238 37

The effects of serotonin receptor antagonists with differential selectivity for the various classes of 5HT receptors (5HT1, 5HT2 and 5HT3) were tested for their effects on the response to aversive brain stimulation. Electrical stimulation was administered to the dorsal part of the periaqueductal gray matter (PAG), one of the main cerebral structures subserving negative reinforcement. Stimulation frequency thresholds for escape responses were recorded before and following administration of the compounds. Ketanserin (0.32-32 mg/kg IP), trazodone (1.0-22 mg/kg), pirenperone (0.032-1.0 mg/kg) and spiperone (0.1-0.2 mg/kg) dose-dependently increased stimulation frequency thresholds necessary to induce escape responses. Opposite effects were observed with mianserin (0.01-32 mg/kg) and metergoline (0.032-10 mg/kg) which decreased threshold for escape. ICS 205-930 (0.01-10 mg/kg), did not affect the stimulation frequency threshold for escape. Prazosin (0.1-22 mg/kg) did not specifically affect aversive brain stimulation. Haloperidol (0.02-1.0 mg/kg) increased the frequency threshold for escape responses but with some motoric side effects. These data show that the various types of 5HT receptors differentially contribute to the control of central aversive systems in rats. It is suggested that blockade of 5HT2 receptors suppresses the central aversive system, whereas blockade of some 5HT1 receptors enhances aversion and overcomes the 5HT2-mediated suppression. Blockade of 5HT3 receptors has no effects. Dopamine receptor blockade further contributes to the suppression of the central aversive system. The relevance of these findings to some pathophysiological mechanisms of anxiety and depressive disorders is discussed.
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PMID:Effects of serotonin receptor antagonists on PAG stimulation induced aversion: different contributions of 5HT1, 5HT2 and 5HT3 receptors. 249 46

MDL 73,147EF (1H-indole-3-carboxylic acid-trans-octahydro-3-oxo-2,6- methano-2H-quinolizin-8-yl-ester methanesulphonate) is a potent and selective 5-HT3 receptor antagonist (pA2 9.8, rabbit heart; pIC50 less than 5, D-2 receptor). The effects of acutely and chronically administered haloperidol and MDL 73,147EF were compared in an electrophysiologic model for antipsychotic activity. Haloperidol, but not MDL 73,147EF, given acutely increased the number of active dopamine neurons in the substantia nigra (A9). Both haloperidol and MDL 73,147EF, given chronically, decreased the number of active ventral tegmental dopamine neurons and the number of active A9 dopamine neurons. The results indicate that MDL 73,147EF may prove useful as an antipsychotic with a unique mechanism of action.
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PMID:Effect of acute and chronic MDL 73,147EF, a 5-HT3 receptor antagonist, on A9 and A10 dopamine neurons. 274 86

Latent inhibition (LI) is a behavioural phenomenon whereby preexposure to a stimulus without reinforcement interferes with the formation of subsequent associations to that stimulus. Using preexposure to a tone stimulus which subsequently serves as a conditioned stimulus for suppression of licking, we have confirmed that LI is disrupted by a low dose of amphetamine. Haloperidol was able to prevent this effect of amphetamine. Ondansetron, a selective and potent 5HT3 receptor antagonist, was also shown to be effective at blocking the amphetamine-induced disruption of LI at a dose of 0.01 mg/kg, but not at 0.1 mg/kg. In addition, it was demonstrated that ondansetron could enhance LI; using only ten preexposures, no LI was obtained in the saline group, but was apparent in animals given ondansetron, an effect which has been previously shown with haloperidol. Haloperidol, at the higher dose used, reduced suppression of licking, however, ondansetron at the effective dose had no such effect. It is concluded that ondansetron is able to attenuate increases in dopamine activity, produced pharmacologically with amphetamine without affecting baseline dopamine activity. The implications of these findings for a possible antipsychotic action of ondansetron are discussed.
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PMID:Antagonism of amphetamine-induced disruption of latent inhibition in rats by haloperidol and ondansetron: implications for a possible antipsychotic action of ondansetron. 785 29

A pharmacologic analysis of the discriminative stimulus of metachlorophenylpiperazine (mCPP) is reported. mCPP and m-trifluoromethylphenylpiperazine generalised, whereas 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole, 6-chloro-2-(1-piperazinyl)-pyrazine, and mesulergine partially generalised to the mCPP discriminative cue. However, although mianserin, methiothepin, ritanserin, mesulergine and N-(1-methyl-5'-indolyl)-N'-(3-pyridyl)urea hydrochloride (SB 200646) all antagonised the effect of 5-hydroxytryptamine (5-HT) on IP3 formation in the rat choroid plexus, they failed to antagonise the mCPP response in the drug discrimination studies. The 5-HT3 receptor antagonist MDL 72222 neither generalised nor antagonised the mCPP cue. These data suggest that neither the 5-HT1A, 5-HT1B, 5-HT1D, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT3, 5-HT5, 5-HT6, nor 5-HT7 receptors are involved. The response does appear to be mediated by a postsynaptic 5-HT receptor, however, because fenfluramine generalised to the cue. Haloperidol generalises, and amphetamine partially antagonises the mCPP discriminative cue and low doses of apomorphine partially generalises to the mCPP cue, which suggests that a decrease in dopamine neurotransmission may also be involved.
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PMID:Pharmacologic evaluation of the discriminative stimulus of metachlorophenylpiperazine. 884 38