DOI hydrochloride

Serotonin (5-HT)2A/2C receptor agonist (2,5-dimethoxy-4-idophenyl)-2-aminopropane hydrochloride (DOI) improves voiding efficiency in the diabetic rat.[Pubmed:25822577]

BJU Int. 2015 Jul;116(1):147-55.

OBJECTIVES: To examine the effects of the serotonin (5-HT)2A/2C receptor agonist (2,5-dimethoxy-4-idophenyl)-2-aminopropane hydrochloride (DOI) on micturition in rats with diabetes mellitus (DM). METHODS: Female Sprague-Dawley rats (n = 16) were divided into two groups: rats with Type 1 DM and age-matched control rats. DM was induced by i.p. injection of streptozotocin (65 mg/kg) and detailed cystometrogram (CMG) studies were performed 8 weeks post-injection in all rats under urethane anaesthesia. The selective 5-HT2A antagonist ketanserin was administered after each DOI dose-response curve was plotted. All drugs were administered i.v. RESULTS: Compared with controls, comprehensive urodynamic studies showed that DM rats had a higher bladder capacity and post-void residual urine volume (PVR), and a markedly lower voiding efficiency. In DM rats, DOI (0.01-0.3 mg/kg) induced significant dose-dependent increases in micturition volume and reductions in PVR, resulting in greater voiding efficiency. CMG measurements showed a dose-dependent increase in high-frequency oscillation (HFO) activity, evidenced by an increased duration of HFOs per voiding. This correlated with the improved voiding efficiency. Ketanserin (0.1 mg/kg) partially or completely reversed the DOI-induced changes. CONCLUSIONS: The HFOs observed in the present study seem to correlate with external urethral sphincter bursting activity during voiding. Bladder voiding efficiency was reduced in DM rats. The 5-HT2A receptor agonist can enhance HFO activity and improves voiding efficiency, and so may represent a new strategy to improve voiding efficiency after DM in experimental studies.

Serotonin and its 5-HT(2) receptor agonist DOI hydrochloride inhibit the oxidative burst in total leukocytes but not in isolated neutrophils.[Pubmed:20149804]

Life Sci. 2010 Mar 27;86(13-14):518-23.

AIMS: Serotonin (5-HT) is capable of reducing the oxidative burst of professional phagocytes. In this study, we investigated whether 5-HT mediates this modulation via 5-HT receptors (5-HTR) or whether this is due instead to 5-HT antioxidative properties. MAIN METHODS: The leukocytes or polymorphonuclear leukocytes (PMNL) were isolated from human blood, and their ability to produce reactive oxygen species (ROS) after 5-HT or its agonist treatment was tested by luminol-enhanced chemiluminescence (CL) analysis. KEY FINDINGS: It was found that 5-HTR(2) agonist DOI hydrochloride does not have any antioxidative properties, despite its ability to inhibit the CL response of activated human total leukocytes. On the other hand, DOI hydrochloride was unable to inhibit the CL response of activated human PMNL. It seems that the reduction of the oxidative burst of professional phagocytes was evoked by the activation of 5-HTR not on the neutrophil surface but on the surface of different leukocytes, which produced anti-inflammatory cytokines with NADPH oxidase activity modulating properties. SIGNIFICANCE: Platelets and activated PMNL are in tight contact at sites of inflammation. 5-HT released from platelets might have a protective function against PMNL-derived oxidative stress and oxidative damages.

Chronic electroconvulsive shock decreases (+/-) 1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane hydrochloride (DOI)-induced wet-dog shake behaviors of dexamethasone-treated rats.[Pubmed:10737422]

Life Sci. 2000 Feb 18;66(13):1271-9.

Electroconvulsive shock (ECS) therapy is considered to be an effective treatment for depression, but its mechanism of action is still unknown. We investigated the effect of chronic ECS in rats treated for 14 days with dexamethasone (Dex), a glucocorticoid receptor agonist. Chronic injection of sesame oil decreased body weight change and increased serotonin (5-HT)-2A receptor number and DOI (5-HT-2A, 2C receptor agonist)-induced wet-dog shake (WDS) behaviors. Dex treatment for 14 days decreased body weight of rats, but repeated ECS did not reverse this decrease. Dex also abolished plasma corticosterone levels, and ECS failed to restore these levels. These results indicate that chronic ECS does not antagonize the effect of Dex. The treatment with Dex increased 5-HT-2A receptor binding density of rat frontal cortex and the number of DOI-induced WDS behaviors. Chronic ECS reduced the enhanced WDS behaviors by Dex but had little effect on receptor density. These results suggest that chronic ECS might suppress 5-HT-2A receptor function at the postreceptor signaling level rather than at the receptor itself, without changing HPA axis function in Dex-treated rats.

Serotonin 5-hydroxytryptamine(2A) receptor activation suppresses tumor necrosis factor-alpha-induced inflammation with extraordinary potency.[Pubmed:18708586]

J Pharmacol Exp Ther. 2008 Nov;327(2):316-23.

The G protein-coupled serotonin 5-hydroxytryptamine (5-HT)(2A) receptor is primarily recognized for its role in brain neurotransmission, where it mediates a wide variety of functions, including certain aspects of cognition. However, there is significant expression of this receptor in peripheral tissues, where its importance is largely unknown. We have now discovered that activation of 5-HT(2A) receptors in primary aortic smooth muscle cells provides a previously unknown and extremely potent inhibition of tumor necrosis factor (TNF)-alpha-mediated inflammation. 5-HT(2A) receptor stimulation with the agonist (R)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane [(R)-DOI] rapidly inhibits a variety of TNF-alpha-mediated proinflammatory markers, including intracellular adhesion molecule 1 (ICAM-1), vascular adhesion molecule 1 (VCAM-1), and interleukin (IL)-6 gene expression, nitric-oxide synthase activity, and nuclear translocation of nuclear factor kappaB, with IC(50) values of only 10 to 20 pM. It is significant that proinflammatory markers can also be inhibited by (R)-DOI hours after treatment with TNF-alpha. With the exception of a few natural toxins, no current drugs or small molecule therapeutics demonstrate a comparable potency for any physiological effect. TNF-alpha-mediated inflammatory pathways have been strongly implicated in a number of diseases, including atherosclerosis, rheumatoid arthritis, psoriasis, type II diabetes, depression, schizophrenia, and Alzheimer's disease. Our results indicate that activation of 5-HT(2A) receptors represents a novel, and extraordinarily potent, potential therapeutic avenue for the treatment of disorders involving TNF-alpha-mediated inflammation. Note that because (R)-DOI can significantly inhibit the effects of TNF-alpha many hours after the administration of TNF-alpha, potential therapies could be aimed not only at preventing inflammation but also treating inflammatory injury that has already occurred or is ongoing.

Effects of the serotonin 5-HT2A/2C receptor agonist DOI and of the selective 5-HT2A or 5-HT2C receptor antagonists EMD 281014 and SB-243213, respectively, on sleep and waking in the rat.[Pubmed:17059817]

Eur J Pharmacol. 2006 Dec 28;553(1-3):163-70.

The effects of the serotonin 5-HT(2A/2C) receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and of the selective 5-HT(2A) or 5-HT(2C) receptor antagonists 7-{4-[2-(4-fluoro-phenyl)-ethyl]-piperazine-1-carbonyl}-1H-indole-3-carbonitrile HCl (EMD 281014) and 5-methyl-1-[[-2-[(2-methyl-3-pyridyl)oxy]-5-pyridyl]carbamoyl]-6-trifluoromethyli ndoline HCl (SB-243213), respectively, on spontaneous sleep were studied in adult rats implanted for chronic sleep recordings. Subcutaneous administration of DOI (0.35-0.7 mmol/kg) significantly increased waking and light sleep and reduced slow wave sleep, rapid-eye-movement (REM) sleep, and the number of REM periods. With subcutaneous EMD 281014 (1.2-4.8 mmol/kg) or SB-243213 (1.2-4.8 mmol/kg) a significant reduction in time spent in REM sleep was also seen. Pretreatment with EMD 281014 prevented the DOI-induced increase of waking and light sleep and the reduction of slow wave sleep. However, REM sleep remained suppressed. SB-243213 failed to reverse the changes of sleep and waking induced by DOI. Thus, on the basis of these results it appears that serotonin 5-HT(2A) receptor mechanisms might be responsible for the DOI-induced effects on waking and slow wave sleep.