Disease relevance of Lopac-M-109

• On the other hand, injection of 5-HT3 receptor agonists (2-methyl 5-HT; 0.86 mg/kg, m-CPG; 8 mg/kg) did not produce hyperalgesia [1].
• The suppressive action of GR38032F on spontaneous sleep apneas is analogous to findings in anesthetized rats in which 5-HT and 2-methyl-5-HT provoked central apneas that were antagonized by GR38032 (Yoshioka et al, JPET 1992; 260:917-924) [2].
• In anaesthetized rats, i. v. administration of alosetron inhibited 2-methyl-5-HT induced bradycardia (Bezold Jarisch index) at 1 and 3 microg kg-1, with an agonist dose ratio of approximately 3.0 at 1.0 microg kg-1, = 3-5) [3].
• These results indicate that ICS 205-930 attenuates hypothermia induced by radiation and 2-Me-5-HT [4].
• 5-Hydroxytryptamine (5-HT; i.p., i.v., s.c.) and 2-methyl-5-HT (2-Me-5-HT; i.p.) but not 5-hydroxyindoleacetic acid (i.p.) or 5-methoxytryptamine (i.p.) induced emesis with very short latency [5].

Psychiatry related information on Lopac-M-109

• 2-Methyl-5-HT produced forward locomotion, rearing, and increased wakefulness, but did not appreciably alter circling, grooming or sniffing [6].
• Methiothepin pretreatment had no effect on the hyperlocomotor response to 2-methyl-5-HT, although methiothepin itself produced an initial increase in spontaneous locomotor activity (for the 60-120 min period) [6].

High impact information on Lopac-M-109

• The actions of ICS 205-930 and 2-methyl-5-HT indicate that the response is mediated by the 5-HT3 receptor [7].
• This response was mimicked by the 5-HT3 receptor agonist, 2-methyl-5-HT, and blocked by the 5-HT3 receptor antagonist, tropisetron [8].
• Interestingly, 2-methyl-5-HT did not evoke chloride secretion in the human intestine but it did in the guinea-pig intestine [8].
• In rats with intact vagi, 2-methylserotonin produced a dose-dependent increase in afferent vagal nerve activity and a dose-dependent decrease in efferent renal sympathetic nerve activity, mean arterial pressure, and heart rate [9].
• Current was blocked by the selective 5-HT3 antagonist ICS 205-930 even in the presence of EtOH, and current activated by a 5-HT3 agonist (2-methyl-5-HT) was potentiated by EtOH [10].

Chemical compound and disease context of Lopac-M-109

• However, the same doses of ondansetron administered i.p. or intraventricularly did not antagonize the hypothermia induced by 10 micrograms 2-Me-5-HT [4].
• Intrathecal application of fluvoxamine maleate and selective 5-HT receptor agonists, i.e., 8-hydroxy-2-(di-n-proplyamino)-tetralin hydrobromide (8-OH-DPAT: 5HT-1 selective) and 2-methyl-5-hydroxytryptamine maleate (2-m-5-HT: 5HT-3 selective), inhibited the spinal cord injury-induced hyperalgesia [11].
• The 5-HT3 receptor agonist, 2-methyl-5-HT, and copper sulfate also induced emesis of short duration [12].
• Our study on the azabicycloalkaneacetamide derivatives showed that 2,3-dihydroindole as the aromatic ring moiety afforded potent 5-HT3 receptor antagonist activity, as judged by blockade of bradycardia induced by i.v. injection of 2-methylserotonin in anesthetized rats [13].
• The metabolite M1 antagonized the 2-methyl-5-HT-induced bradycardia in anesthetized rats with an ED50 value of 10.5 micrograms/kg, i.v., and inhibited the cisplatin-induced emesis in ferrets with a potency approximately 25 times that of mosapride [14].

Biological context of Lopac-M-109

• Displacing ligands produced a pharmacologic profile of the [3H]RS-42358-197 binding site consistent with it being a 5-HT3 receptor: (R)-YM060 > (S)-zacopride > (R)-zacopride > MDL 72222 > 2-methyl-5-HT [15].
• Iontophoresis of 2-methyl-5-HT also diminished CA1 postsynaptic field potentials evoked by electrical stimulation of the Schaffer collaterals [16].
• 4. The vasoconstrictions produced by 5-HT and 2-methyl-5-HT were blocked by ketanserin [17].
• 2-Me-5-HT, however, failed to modify either female or male rat sexual activity [18].
• CP-99,994 (1 mg kg-1, i.v.) did not alter baseline cardiovascular and respiratory parameters and it failed to block the characteristic heart rate, blood pressure and respiratory rate/depth changes in response to i.v. 2-methyl-5-HT challenge (von Bezold-Jarisch reflex) [19].

Anatomical context of Lopac-M-109

• 7. The capacity of the 5-HT3 receptor agonist, 2 methyl-5-HT, to enhance the electrically evoked release of tritium was not altered in hypothalamus, hippocampus, and frontal cortex slices prepared from befloxatone-treated guinea-pigs, but was significantly attenuated in the paroxetine group also treated for 21 days.(ABSTRACT TRUNCATED AT 400 WORDS)[20]
• 5-HT and 2-methyl-5-HT induced dose-dependent depolarizations of rat isolated vagus nerve with EC50 values of 2.53 (1.93-3.33) x 10(-6) and 4.03 (2.87-5.66) x 10(-6) M, respectively [21].
• 3. In hypothalamus slices, this response was lost when 2-methyl-5-HT was introduced 20 min before the stimulation, thus indicating that these 5-HT3 receptors desensitize rapidly [22].
• 2-methyl-5-HT had no effect on the tracheal smooth muscle [17].
• 1. Despite the fact that 5-hydroxytryptamine (5-HT)-induced contractions of the rabbit isolated renal artery are mediated by a receptor belonging to the heterogeneous 5-HT1-like category, we observed that the so-called selective 5-HT3 receptor agonist, 2-methyl-5-HT, caused a concentration-dependent contraction of this vessel [23].

Associations of Lopac-M-109 with other chemical compounds

• All antagonist competition curves were steep (pseudo-Hill coefficients not lower than 1), monophasic, and best fit for a one-site model; 5-HT and 2-methyl-5-HT produced pseudo-Hill coefficients of 1.2-1 [24].
• alpha-Methyl-5-hydroxytryptamine (alpha-Me-5-HT; 2) and 2-methyl-5-hydroxytryptamine (2-Me-5-HT; 3) are considered to be 5-HT2-selective and 5-HT3-selective agents, respectively [25].
• This study was therefore undertaken to analyze the effects of 2-methyl-5-HT in the renal artery segments, either quiescent or precontracted with U46619 (10(-7) M). alpha-Methyl-5-HT and 5-methoxytryptamine, which have high affinities for 5-HT2 and 5-HT4 receptors, respectively, were used for comparison [23].
• Phenylbiguanide (PBG) and 2-methyl-5-hydroxytryptamine (2-methyl-5-HT) were found to mimic the effects of 5-HT on the vagus nerve [26].
• 6. In the presence of a high concentration of (10 microM) 5-methoxytryptamine the subsequent addition of 2-methyl-5-HT (3-10 microM) but not 5-methoxytryptamine (10 microM) facilitated peristalsis; the effect of 3 microM 2-methyl-5-HT was significantly decreased by 2 microM ondansetron [27].

Gene context of Lopac-M-109

• The effect of 2-Me-5-HT is blocked by 5-HT2 and not by 5-HT3 receptor antagonists, indicating that 5-HT3 receptors do not directly or indirectly take part in PI hydrolysis in the spinal cord [28].
• The efficacy for different agonists rated: alpha-methyl-5-HT (5-HT2) = 5-HT (non-selective) = 2-methyl-5-HT (5-HT3) >> sumatriptan (5-HT1), and the potency as: sumatriptan = 5-HT > 5-HT > alpha-methyl-5-HT > 2-methyl-5-HT [29].
• No interaction was encountered between 2-methyl-5-HT and MDL72222, suggesting an absence of 5-HT3 receptors [29].
• Scratching was also elicited by the 5-HT2 receptor agonist alpha-methylserotonin, but not by the 5-HT1A receptor agonist R(+)-8-hydroxy-N,N-dipropyl-2-aminotetralin nor the 5-HT3 receptor agonists 2-methylserotonin and 1-phenylbiganide [30].
• These responses are antagonized by ICS 205-930 and mimicked by 2-methyl-5-HT and anti-idiotypic antibodies [31].

Analytical, diagnostic and therapeutic context of Lopac-M-109

• To study the influence of dietary sodium intake on 2-methylserotonin-induced vagal reflex responses, we performed experiments in rats fed either a high or low sodium diet [9].
• 2. The selective 5-HT3 agonist, 2-methyl-5-HT, introduced 8 min before the electrical stimulation, enhanced in a concentration-dependent manner the evoked release of [3H]-5-HT in the three brain regions studied [22].
• In mice tested with i.t. administration of 2-methyl-5-HT, only 5-HT3 receptor AODN attenuated analgesia [32].
• Alpha-methylserotonin (1 microM) if added alone to the perfusion medium had no effect on 1 mM L-GLU-evoked release of NE but reversed the inhibition induced by 1 microM 2-methylserotonin [33].
• On day 6, all mice were injected i.t. with 70.5 nmol of 5-HT, 44.4 nmol of CGS-12066A, or 49 nmol of 2-methyl-5-HT by lumbar puncture [32].

References