Pharmacology of a novel selective 5-hydroxytryptamine1B receptor antagonist, AR-A000002

  title={Pharmacology of a novel selective 5-hydroxytryptamine1B receptor antagonist, AR-A000002},
  author={Carina Stenfors and Teresa Hallerb{\"a}ck and Lars-Gunnar Larsson and Carin Wallsten and Svante B. Ross},
  journal={Naunyn-Schmiedeberg's Archives of Pharmacology},
The terminal 5-HT1B autoreceptors have attracted great pharmacological interest since they are potential targets for compounds modifying serotonergic neurotransmission. In the present work the in vivo biochemical properties of AR-A000002 ((R)-N-[5-methyl-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydro-2-naphthyl]-4-morpholinobenzamide), a novel selective 5-HT1B receptor antagonist, are reported.The effects of AR-A000002 on: 5-HT metabolism was measured as the ratio between 5-HIAA and 5-HT… 

[N-methyl-3H3]AZ10419369 Binding to the 5-HT1B Receptor: In Vitro Characterization and in Vivo Receptor Occupancy

In vitro and in vivo evaluation of tritiated 5- methyl-8-(4-methyl-piperazin-1-yl)-4-oxo-4H-chromene-2-carboxylicacid (4-morpholin-4-yl-phenyl)-amide, a potent 5-HT1B radiotracer, show it is a useful preclinical tool for investigating 5- HT1B receptor occupancy for novel compounds targeting this receptor.

Repeated administration of the 5-HT1B receptor antagonist SB-224289 blocks the desensitisation of 5-HT1B autoreceptors induced by fluoxetine in rat frontal cortex

It is concluded that the effects obtained when 5-HT1B autoreceptor antagonists are administered acutely together with SSRIs may not be maintained after repeated administration.

High-resolution imaging of brain 5-HT 1B receptors in the rhesus monkey using [11C]P943.

Involvement of the 5-HT1A and the 5-HT1B receptor in the regulation of sleep and waking

Overall, most studies support the possibility that stimulation of postsynaptic 5-HT1A receptors, e.g., via systemic administration of a high dose of agonists increases wakefulness and decreases sleep and the mechanism by which 5- HT1B receptors affect state modulation remain elusive.



Behavioral Pharmacology of AR-A000002, a Novel, Selective 5-Hydroxytryptamine1B Antagonist

Data suggest utility for 5-HT1B antagonists in the treatment of both anxiety and affective disorders.

5-HT 1B/D receptor antagonists.

  • P. Pauwels
  • Biology, Chemistry
    General pharmacology
  • 1997

Synergism between 5-HT1B/1D and 5-HT1A receptor antagonists on turnover and release of 5-HT in guinea-pig brain in vivo

Extracellular 5-HIAA seems to be a better marker than 5-HT itself for the evoked5-HT release when the reuptake mechanism is intact and the synergistic effect of the two receptor antagonists on the 5-ht turnover and the terminal release of 5- HT indicate somatodendritic 5-HCIAA release and stimulation of inhibitory 6-HT1A receptors at this level.

The 5-HT1A receptor agonist, 8-OH-DPAT, preferentially activates cell body 5-HT autoreceptors in rat brain in vivo

Findings provide direct neurochemical evidence that by preferentially stimulating somatodendritic 5-HT1A receptors, 8-OH-DPAT inhibits the 5- HT neuronal impulse flow, thereby effectuating decreased terminal 5-hydroxytryptamine synthesis and release.

Effects of a selective 5-HT reuptake blocker, citalopram, on the sensitivity of 5-HT autoreceptors: Electrophysiological studies in the rat brain

It is concluded that long-term CIT treatment enhances 5-HT neurotransmission by desensitizing both the somatodendritic and terminal 5- HT autoreceptors.

Failure to detect in vivo inverse agonism of the 5-HT1B receptor antagonist SB-224289 in 5-HT-depleted guinea-pigs

It is concluded that no constitutive activity of 5- HT1B autoreceptors (5-HIAA formation) or 5-HT1B heteroreceptorors (rectal temperature) could be detected under the in vivo experimental conditions used.