Disease relevance of Spiroxatrine

• Similarly, only the 5-HT1A antagonists, spiroxatrine and spiperone, attenuated the hyperalgesia induced by intradermally injected serotonin [1].
• DPAT-induced ocular hypotension was inhibited by pretreatment with spiroxatrine, a 5-HT(1A)and alpha(2C)receptor antagonist, but not spiperone, a 5-HT(2A)receptor antagonist [2].
• The 5-HT1 receptor antagonists, pindolol and spiroxatrine, the 5-HT3 receptor antagonist MDL 72222 and the alpha 2-adrenoceptor blocking agent idazoxan failed to antagonize the tachycardia induced by 5-HT [3].

Psychiatry related information on Spiroxatrine

• Finally, although spiroxatrine (0.1 and 1 mg/kg, -45 min s.c.) inhibited the response to 8-OH-DPAT, this inhibition may also be non-specific since spiroxatrine strongly reduced spontaneous locomotor activity [4].

High impact information on Spiroxatrine

• Spiroxatrine was identified as a moderately potent (K:(i)=118 nM) but non-selective agonist at the human nociceptin/orphanin FQ receptor, ORL1 [5].
• Moreover, the good affinity of [125I] rauwolscine-OHPC binding sites for spiroxatrine, yohimbine, WB 4101, the relatively good affinity for prazosin (Ki =37.4 nM) and the affinity ratio prazosin/oxymetazoline (37.4/43.4=0.86) were consistent with an alpha2C selective labelling of [125I]rauwolscine-OHPC [6].
• In contrast to sigma ligands and other reference compounds, the 5-HT1A agonists buspirone, 8-OH-DPAT and spiroxatrine dose-dependently produced BMY 14802-like discriminative stimulus effects [7].
• The inhibition was blocked by spiroxatrine indicating it was mediated by 5-HT1A receptors [8].
• 3. The putative 5-HT1A antagonists, spiroxatrine (1-30 mg kg-1, p.o.), (+/-)-pindolol (30 mg kg-1, p.o.) and methiothepin (3-10 mg kg-1, p.o.), each attenuated the 8-OH-DPAT (3 mg kg-1, s.c.)-induced increase in mobility [9].

Biological context of Spiroxatrine

• However, the decreases in blood pressure induced by naftopidil were only partly antagonized by spiroxatrine [10].
• The compounds (10(-12)-10(-7) mol bolus injection) neither enhanced basal flow nor evoked vasodilatation in kidneys preconstricted by 27 mM KCl, 1.5 mM BaCl2 or 10(-6) M prostaglandin (PG)F2 alpha, but evoked a dose-dependent, reversible and spiroxatrine-resistant increase in vasodilatation of organs preconstricted by 6 x 10(-7) M noradrenaline [11].

Anatomical context of Spiroxatrine

• Central administration of spiroxatrine through the vertebral artery shifted the dose-response curves of both drugs markedly and in a dose-dependent manner to the right, while the hypotensive response to the peripheral vasodilator nitroglycerin remained unchanged [12].
• The effect of 5 micrograms 8-OH-DPAT on retention latencies was completely antagonized by 1 microgram/microliter spiroxatrine, a 5-HT1A receptor antagonist, infused into the dorsal hippocampus 5 min before 8-OH-DPAT [13].
• A dose-response test with both drugs was performed before and after administration of spiroxatrine (3 and 10 nmol/kg); the latter was given through the vertebral artery, thus delivering the antagonist to the brain stem [12].
• The effect of buspirone on corticotropin-releasing factor (CRF) and stress-stimulated cecal motility and its antagonism by 5-HT1A (spiroxatrine) and sigma (BMY 14802) antagonists were evaluated by electromyography in rats equipped with chronically implanted electrodes on the cecum and a small catheter into the right lateral ventricle of the brain [14].

Associations of Spiroxatrine with other chemical compounds

• The effects of spiroxatrine, a putative antagonist with selectivity for the serotonin (5-HT)1A receptor, were compared with compounds believed to function as agonists at the 5-HT1A receptor [15].
• Spiperone and spiroxatrine, D2 antagonists with high 5-HT1A affinity, also inhibited 8-OH-DPAT-induced STFs [16].
• When phentolamine (500 nM) is included to block alpha receptors and DPAT (100 nM) or spiroxatrine (500 nM) is included to block 5-HT1A receptors, specific binding is exclusively to sites with drug affinities characteristic of 5-HT1B receptors [17].
• Pindolol, spiperone, spiroxatrine and NAN-190 all have a high affinity for the 5-HT1A receptor [18].
• In the pithed rat, the dose-pressor response curves to both 5-HT and DOI were unaffected by MDL 72222 (5-HT3 receptor antagonist), spiroxatrine or (+/-)-pindolol (5-HT1A receptor antagonists), idazoxan (alpha 2-adrenoceptor blocking agent) and AR-C 239 (alpha 1-adrenoceptor blocking agent) [19].

Gene context of Spiroxatrine

• In anaesthetized rats, the 5-HT1A antagonist, spiroxatrine (1 mg/kg), and the 5-HT3 receptor antagonist, MDL72222 (0.3 mg/kg), selectively diminished the hypotensive phase without affecting the pressor phase [20].
• The 5-HT1A agonist 8-hydroxy-2-(di-N-propylamine)tetralin hydrobromide mimicked, whereas the 5-HT1A antagonist spiroxatrine blocked, these hyperpolarizing responses [21].
• Whereas spiroxatrine (0.5 mg/kg s.c.) blocked the effect of buspirone on the colonic hypermotility induced by i.c.v. injection of CRF, BMY 14802 at a similar dose (0.5 mg/kg s.c.) was unable to block the action of buspirone [14].
• Metitepine and methysergide antagonized the inhibitory effect of 5-HT, whereas spiroxatrine, propranolol, ketanserin and ICS 205-930 did not [22].
• The administration of the 5HT1A agonist (8-hydroxy 2-n-dipropylamino tetralin) resulted in a significant increase in plasma prolactin and that of the specific 5HT1A antagonist spiroxatrine had the opposite effect [23].

Analytical, diagnostic and therapeutic context of Spiroxatrine

• Seizure discharge activity was attenuated by the microinjection of the 5-HT1A agonist, 8-hydroxy-2-(di-N-propylamino)tetralin(8-(OH)-DPAT) and augmented by the specific 5-HT1A antagonist, spiroxatrine in the contralateral hippocampal CA-3 region [24].

References