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Chemical Compound Review

AC1MIUNY     N-(8-methyl-8- azabicyclo[3.2.1]oct-3-yl)- 2...

Synonyms: CHEMBL539261, SureCN7342367, DAU 6215, LS-32715, C16H20N4O2.HCl, ...
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Disease relevance of ITASETRON

  • The results demonstrate that DAU 6215 is a highly effective and long-lasting inhibitor of cytotoxic treatment-induced emesis in different animal species [1].
  • 4. In vivo studies--neurotransmitter functions: a) Monoaminergic transmission: reserpine-induced hypothermia in mice was not antagonized by DAU 6215 (0.01-1 mg/kg i.p.).(ABSTRACT TRUNCATED AT 250 WORDS)[2]
  • 3. In vivo studies--general behaviour: In mice, DAU 6215 was well tolerated up to 100 mg/kg p.o. and 30 mg/kg i.v. The only noticeable symptom was mydriasis [2].
  • DAU 6215 was inactive in (iv) the elevated plus maze, (v) conflict test and (vi) emotional hypophagia in rats and in (vii) the four plates test, (viii) staircase test and (ix) stress-induced hyperthermia in mice [3].

Psychiatry related information on ITASETRON

  • Conversely, a repeated IP administration of 10 micrograms/kg DAU 6215 for 3 weeks significantly improved task performance of the aged animals as compared to that displayed by the old rats treated with the vehicle [4].
  • In line with the theory that hyperactivity of the mesolimbic dopaminergic system is involved in psychosis, the results suggest that DAU 6215 may be useful in the treatment of psychotic disorders, possibly with limited extrapyramidal effects [5].
  • Itasetron (DAU 6215) prevents age-related memory deficits in the rat in a multiple choice avoidance task [6].
  • Effect of DAU 6215, a novel 5-HT3 receptor antagonist, on scopolamine-induced amnesia in the rat in a spatial learning task [7].

High impact information on ITASETRON

  • The effects of the new 5-HT3 receptor antagonist, DAU 6215, on aged rats' cognition were assessed in the Morris water maze task [4].
  • Twenty-four hours after the last injection, the basal extracellular concentrations of DA in the nucleus accumbens of rats given DAU 6215 were significantly lower than in saline-treated rats [5].
  • Similarly, DAU 6215 did not affect the membrane depolarization and decrease in amplitude of the afterhyperpolarization, elicited by the activation of putative 5-HT4 receptors [8].
  • 2. Administration of DAU 6215, even at concentrations several hundred fold its Ki, did not affect the cell membrane properties of pyramidal neurones, nor modify extracellularly recorded synaptic potentials, evoked by stimulating the Schaffer's collaterals [8].
  • Pretreatment with DAU 6215 did not modify the inhibitory effect of apomorphine on the firing rate of midbrain DA neurons [9].

Biological context of ITASETRON

  • DAU 6215 did not exhibit any effect either on motor and exploratory activity or in the traction test in mice up to 30 mg/kg i.p. In the open field test in rats, DAU 6215 (0.01 and 10 mg/kg p.o.) failed to modify the behavioural parameters considered, with the exception of a decrease in defecations at 10 mg/kg [2].

Anatomical context of ITASETRON


Associations of ITASETRON with other chemical compounds

  • The efficacies of BIMU 8 and cisapride were comparable (133 +/- 9% and 124 +/- 8% of the maximal 5-HT efficacy, respectively), whereas BIMU 1 and DAU 6215 elicited, respectively, only 72 +/- 11% and 16 +/- 4% of the maximal 5-HT effect [10].
  • The rank order of their potencies as compared with those of 5-HT and cisapride was as follows: BIMU 8 = cisapride greater than 5-HT greater than BIMU 1 greater than DAU 6215 [10].

Gene context of ITASETRON

  • The cardiovascular effects of DAU 6215, a novel 5-HT3 receptor antagonist were studied [11].
  • Two of the compounds, BIMU 1 and BIMU 8, which show prokinetic activity in various animal models, were also good agonists at the 5-HT4 receptors, whereas DAU 6215, a drug devoid of prokinetic activity, was only a weak, partial agonist at 5-HT4 receptors [10].
  • 2. In vitro studies--receptor binding: DAU 6215 showed a high affinity for 5-HT3 receptors (Ki, nmol/l: 3.8) without any significant affinity for other serotonergic, adrenergic or dopaminergic receptors [2].

Analytical, diagnostic and therapeutic context of ITASETRON


  1. Antiemetic activity of the new 5-HT3 antagonist DAU 6215 in animal models of cancer chemotherapy and radiation. Sagrada, A., Turconi, M., Bonali, P., Schiantarelli, P., Micheletti, R., Montagna, E., Nicola, M., Algate, D.R., Rimoldi, E.M., Donetti, A. Cancer Chemother. Pharmacol. (1991) [Pubmed]
  2. Effects on general behaviour and neurotransmitter functions of a new 5-hydroxytryptamine3 receptor antagonist with potential therapeutic relevance in central nervous system disturbances. Rizzi, C.A., Prudentino, A., Giraldo, E. Arzneimittel-Forschung. (1993) [Pubmed]
  3. The effect of DAU 6215, a novel 5HT-3 antagonist, in animal models of anxiety. Borsini, F., Brambilla, A., Cesana, R., Donetti, A. Pharmacol. Res. (1993) [Pubmed]
  4. DAU 6215, a novel 5-HT3 receptor antagonist, improves performance in the aged rat in the Morris water maze task. Pitsikas, N., Brambilla, A., Borsini, F. Neurobiol. Aging (1993) [Pubmed]
  5. Selective reduction of extracellular dopamine in the rat nucleus accumbens following chronic treatment with DAU 6215, a 5-HT3 receptor antagonist. Invernizzi, R., Pozzi, L., Samanin, R. Neuropharmacology (1995) [Pubmed]
  6. Itasetron (DAU 6215) prevents age-related memory deficits in the rat in a multiple choice avoidance task. Pitsikas, N., Borsini, F. Eur. J. Pharmacol. (1996) [Pubmed]
  7. Effect of DAU 6215, a novel 5-HT3 receptor antagonist, on scopolamine-induced amnesia in the rat in a spatial learning task. Pitsikas, N., Brambilla, A., Borsini, F. Pharmacol. Biochem. Behav. (1994) [Pubmed]
  8. Effects of DAU 6215, a novel 5-hydroxytryptamine3 (5-HT3) antagonist on electrophysiological properties of the rat hippocampus. Passani, M.B., Pugliese, A.M., Azzurrini, M., Corradetti, R. Br. J. Pharmacol. (1994) [Pubmed]
  9. Chronic treatment with DAU 6215, a new 5-HT3 receptor antagonist, causes a selective decrease in the number of spontaneously active dopaminergic neurons in the rat ventral tegmental area. Prisco, S., Pessia, M., Ceci, A., Borsini, F., Esposito, E. Eur. J. Pharmacol. (1992) [Pubmed]
  10. Azabicycloalkyl benzimidazolone derivatives as a novel class of potent agonists at the 5-HT4 receptor positively coupled to adenylate cyclase in brain. Dumuis, A., Sebben, M., Monferini, E., Nicola, M., Turconi, M., Ladinsky, H., Bockaert, J. Naunyn Schmiedebergs Arch. Pharmacol. (1991) [Pubmed]
  11. Influence of DAU 6215, a novel 5-HT3 receptor antagonist, on the cardiovascular system in anaesthetized and pithed rats. Malinowska, B., Pawlak, D., Buczko, W. Agents Actions (1992) [Pubmed]
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