RU 24969
目录号 : GC37569
A 5-HT1A and 5-HT1B receptor agonist
Cas No.:66611-26-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
RU-24969 is an agonist of the serotonin (5-HT) receptor subtypes 5-HT1A and 5-HT1B.1 It binds to 5-HT1A and 5-HT1B receptors (IC50s = 9.5 and 6.6 nM, respectively) and is selective for these receptors over 5-HT2 receptors in cell-free assays (IC50 = 5,120 nM). RU-24969 inhibits tritium efflux induced by the 5-HT antagonist methiothepin in tritium-preloaded rat frontal cortex slices (pA2 = 6.27). In vivo, RU-24969 (3 mg/kg) potentiates cocaine-induced increases in nucleus accumbens dopamine levels, as well as the reinforcing effects of cocaine self-administration, in rats.2
1.Middlemiss, D.N.The putative 5-HT1 receptor agonist, RU 24969, inhibits the efflux of 5-hydroxytryptamine from rat frontal cortex slices by stimulation of the 5-HT autoreceptorJ. Pharm. Pharmacol.37(6)434-437(1985) 2.Parsons, L.H., Koob, G.F., and Weiss, F.RU 24969, a 5-HT1B/1A receptor agonist, potentiates cocaine-induced increases in nucleus accumbens dopamineSynapse32(2)132-135(1999)
| Cas No. | 66611-26-5 | SDF | |
| Canonical SMILES | COC1=CC=C2C(C(C3=CCNCC3)=CN2)=C1 | ||
| 分子式 | C14H16N2O | 分子量 | 228.29 |
| 溶解度 | DMSO: ≥ 30 mg/mL (131.41 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
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1 mg | 5 mg | 10 mg |
| 1 mM | 4.3804 mL | 21.902 mL | 43.8039 mL |
| 5 mM | 0.8761 mL | 4.3804 mL | 8.7608 mL |
| 10 mM | 0.438 mL | 2.1902 mL | 4.3804 mL |
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动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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2.
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Reciprocal cross-sensitization between cocaine and RU 24969 in male and female preweanling rats
Pharmacol Biochem Behav 2021 Oct;209:173265.PMID:34437872DOI:10.1016/j.pbb.2021.173265.
Neuronal adaptations involving dopaminergic, glutamatergic, and serotonergic neurotransmitter systems are responsible for behavioral sensitization. Because of common underlying mechanisms, cross-sensitization between compounds of different drug classes can be observed. The purpose of the present study was to determine whether a one- or four-day pretreatment regimen of RU 24969 (a 5-HT1A/1B receptor agonist) would reciprocally cross-sensitize with cocaine or methamphetamine in male and female preweanling rats. Rats were pretreated with RU 24969 (0 or 5 mg/kg) for 4 days (PD 17-20) and then challenged with cocaine (10 or 20 mg/kg) or methamphetamine (1 or 2 mg/kg) on PD 22. Reciprocal cross-sensitization was also assessed (i.e., rats were pretreated with psychostimulants and tested with RU 24969). In a follow-up experiment, the ability of RU 24969 and cocaine to reciprocally cross-sensitize was assessed using a one-day pretreatment regimen. Reciprocal cross-sensitization between cocaine and RU 24969 was evident in preweanling rats, whereas methamphetamine and RU 24969 did not cross-sensitize. When a one-trial pretreatment regimen was used, cross-sensitization was only detected when rats were pretreated with RU 24969 and tested with cocaine, but not the reverse. In sum, the present results show that the nonselective 5-HT1A/1B receptor agonist RU 24969 cross-sensitizes with cocaine, but not methamphetamine, in preweanling rats. This dichotomy may be a function of cocaine having a greater affinity for the serotonin transporter than methamphetamine.
Effects of repeated RU 24969 treatment on the locomotor activity, motoric capacity, and axillary temperatures of male and female preweanling rats
Behav Brain Res 2021 Feb 1;398:112982.PMID:33166571DOI:10.1016/j.bbr.2020.112982.
Serotonin (5-HT) 1A and 1B receptors have been implicated in behavioral sensitization, but adult rats appear to develop tolerance to RU 24969 (a 5-HT1A/1B receptor agonist) rather than a sensitized response. The purpose of the present study was to determine whether a one- or four-day pretreatment regimen of RU 24969 would cause sensitization or tolerance in male and female preweanling rats. Depending on experiment, rats were pretreated with RU 24969 (0, 2.5, or 5 mg/kg) for 1 or 4 days (PD 17-20), while testing with lower or higher doses of RU 24969 occurred on PD 22. Locomotor activity, motoric capacity, and axillary temperatures were recorded. The role of Pavlovian contextual conditioning was assessed by administering RU 24969 to rats in either the home cage or a novel environment. On the first pretreatment day, RU 24969 caused both an increase in forward locomotion and motoric impairment, along with a substantial decrease in axillary temperatures. Repeated treatment with the same dose of RU 24969 caused all three dependent measures to show a tolerance response. When given a higher dose of RU 24969 on the test day, the responses lost due to repeated drug treatment were fully (locomotor activity) or partially (motoric capacity and axillary temperatures) reinstated. There was no evidence of behavioral tolerance. Results are consistent with the hypothesis that a subsensitivity of 5-HT1A/1B receptors is at least partially responsible for the tolerance caused by RU 24969, but dispositional tolerance cannot be excluded as a contributing factor.
RU 24969-produced adipsia and hyperlocomotion: differential role of 5HT 1A and 5HT 1B receptor mechanisms
Pharmacol Biochem Behav 2014 Sep;124:1-4.PMID:24844705DOI:10.1016/j.pbb.2014.05.008.
RU 24969 is a widely used, but non-selective, 5-HT1B/1A agonist that decreases fluid consumption and increases forward locomotion. The mechanism underlying these behavioural responses is not, however, well understood. Accordingly, effects of the selective 5-HT1A and 5-HT1B antagonists, WAY 100635, and GR 127935, respectively, on these two responses to RU 24969 were determined. RU 24969 (0.03-3.0mg/kg, s.c.) dose-dependently decreased water consumption in water deprived rats. This effect was attenuated by GR 127935 (3.0mg/kg), but not by WAY 100635 (1.0mg/kg). RU 24969 (0.3-3.0mg/kg) dose-dependently increased forward locomotion but a higher dose was required to produce this response than the adipsic response. The increased locomotor response was attenuated by WAY 100635 (1.0mg/kg), but not GR 127935 (3.0mg/kg). These results suggest that RU 24969-induced adipsia is mediated by 5-HT1B mechanisms, while RU 24969-induced hyperlocomotion is mediated by 5-HT1A mechanisms.
Evidence that RU 24969-induced locomotor activity in C57/B1/6 mice is specifically mediated by the 5-HT1B receptor
Br J Pharmacol 1993 Dec;110(4):1621-9.PMID:8306109DOI:10.1111/j.1476-5381.1993.tb14010.x.
1. The behavioural effects of the 5-HT1B receptor agonists, RU 24969 and CGS 12066B, have been investigated in C57/B1/6 mice. 2. RU 24969 (1-30 mg kg-1) produced intense and prolonged hyperlocomotion and other behavioural changes. 3. CGS 12066B caused similar effects, but they were much less pronounced, inconsistent and transient irrespective of whether this drug was given i.p. (1-15 mg kg-1) or i.c.v. (0.2-40 micrograms). However, CGS 12066B (7.5 and 15 mg kg-1) caused a dose-related inhibition of RU 24969 (7.5 mg kg-1)-induced hyperlocomotion indicating that the former is a 5-HT1B partial agonist. 4. RU 24969 (7.5 mg kg-1 i.p.)-induced hyperlocomotion was inhibited by the (-)-, but not (+)-isomers of pindolol (4 mg kg-1) and propranolol (20 mg kg-1) but not by metoprolol (10 mg kg-1) or ICI 118,551 (5 mg kg-1), consistent with an involvement of 5-HT1A or 5-HT1B receptors. 5. The response was not altered by the selective 5-HT1A receptor antagonist, WAY 100135 (5 mg kg-1, s.c.), the 5-HT2A/5-HT2C receptor antagonist, ritanserin (0.1 mg kg-1), the selective 5-HT3 receptor antagonist, ondansetron (1 mg kg-1) or the non-selective 5-HT receptor antagonists methysergide (3 mg kg-1) and metergoline (3 mg kg-1). 6. Although spiroxatrine (0.1 mg kg-1) and ketanserin (1 mg kg-1) inhibited RU 24969-induced hyperlocomotion, these effects were probably due to antagonism of dopamine D2 receptors and alpha 1-adrenoceptors respectively. 7. Taken together, these results indicate that RU 24969-induced hyperlocomotion results specifically from activation of central 5-HTIB receptors.8. Lesioning of 5-HT neurones with 5,7-dihydroxytryptamine (75 microg, i.c.v.) or depletion with pchlorophenylalanine(200 mg kg-1, i.p. for 14 days) had no effect on RU 24969-induced hyperlocomotiondemonstrating that the 5-HTIB receptors involved are postsynaptic and that they do not show super sensitivity.9. The involvement of other monoamine neurotransmitter systems in RU 24969-induced hyperlocomotionwas also examined. The response was inhibited by the al-adrenoceptor antagonist, prazosin(1 mg kg-1), the dopamine DI receptor antagonist, SCH 23390 (0.05 mg kg-1) and the dopamine D2 receptor antagonist, BRL 34778 (0.03 mg kg-1), but not by the M2-adrenoceptor antagonist, idazoxan(1 mg kg-1). Lesioning noradrenergic neurones with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine(100 mg kg-1) markedly attenuated this behaviour. These results show that the hyperlocomotion is expressed via noradrenergic and dopaminergic neurones acting on alpha 1-adrenoceptors, DI and D2 receptors.10. RU 24969 decreased brain concentrations of 5-hydroxyindoleacetic acid whilst simultaneously increasing 5-HT, consistent with the reduction of 5-HT neuronal activity by activation of 5-HTlA and 5-HTIB autoreceptors. RU 24969 increased brain 3-methoxy-4-hydroxyphenylglycol, but not noradrenaline, concentrations which supports the involvement of noradrenergic neurones in the expression of hyperlocomotion. RU 24969 did not alter dopamine, dihydroxyphenylacetic acid or homovanillic acid concentrations in the nucleus accumbens suggesting that the dopaminergic neurones terminating there are not directly involved.
Serotonin 5-HT1A and 5-HT1B receptors co-mediate the RU 24969-induced locomotor activity of male and female preweanling rats
Pharmacol Biochem Behav 2020 Feb;189:172857.PMID:31958472DOI:10.1016/j.pbb.2020.172857.
The serotonin (5-HT) 1A/1B agonist RU 24969 robustly increases the locomotor activity of adult male rats and mice; however, studies using selective antagonists alternately report that 5-HT1A, 5-HT1B, or both receptor types mediate RU 24969's locomotor activating effects. The purpose of the present study was to extend these past findings by administering a selective 5-HT1 agonist and/or antagonists to male and female preweanling rats. This age group was tested because younger rats often exhibit psychopharmacological responses that are quantitatively or qualitatively different from adult rats. In a series of experiments, male and female preweanling rats were pretreated with vehicle, the 5-HT1A antagonist WAY 100635 (0.5, 1, 5, or 10 mg/kg), or the 5-HT1B antagonists NAS-181 (5 or 10 mg/kg) or SB 216641 (5 or 10 mg/kg) 30 min before assessment of locomotor activity. Rats were injected with saline or RU 24969 immediately prior to testing. Results showed that RU 24969 (0.625, 1.25, 2.5, or 5 mg/kg) significantly increased the locomotor activity of both male and female preweanling rats (no sex differences were apparent). Antagonism of either the 5-HT1A or the 5-HT1B receptor was sufficient to significantly reduce the locomotor activity of RU 24969-treated preweanling rats. Unexpectedly, NAS-181 did not act as a silent receptor antagonist, as both doses of NAS-181 significantly increased the locomotor activity of saline-treated preweanling rats. In sum, the present results show that both the 5-HT1A and 5-HT1B receptor systems mediate locomotion during the late preweanling period, and this mediation does not vary according to sex.