8-Hydroxy-DPAT hydrobromide

5-HT1A Receptor Function Makes Wound Healing a Happier Process.[Pubmed:30618734]

Front Pharmacol. 2018 Dec 11;9:1406.

Skin wound healing is a multistage phenomenon that is regulated by cell-cell interplay and various factors. Endogenous serotonin is an important neurotransmitter and cytokine. Its interaction with the serotonin 1A receptor (5-HTR1A) delivers downstream cellular effects. The role of serotonin (5-hydroxytryptamine, 5-HT) and the 5-HT1A receptor has been established in the regeneration of tissues such as the liver and spinal motor neurons, prompting the investigation of the role of 5-HT1A receptor in skin healing. This study assessed the role of 5-HT1A receptor in excisional wound healing by employing an excisional punch biopsy model on 5-Ht1a receptor knockout mice. Post-harvest analysis revealed 5-Ht1a receptor knockout mice showed impaired skin healing, accompanied by a greater number of F4/80 macrophages, which prolongs the inflammatory phase of wound healing. To further unravel this phenomenon, we employed the 5-HT1A receptor agonist [(R)-(+)-8-Hydroxy-DPAT hydrobromide] as a topical cream treatment in an excisional punch biopsy model. The 5-HT1A receptor agonist treated group showed a smaller wound area, scar size, and improved neovascularization, which contributed to improve healing outcomes as compared to the control. Collectively, these findings revealed that serotonin and 5-HT1A receptor play an important role during the healing process. These findings may open new lines of investigation for the potential treatment alternatives to improve skin healing with minimal scarring.

Differential effects of (R)-, (R, S)- and (S)-8-hydroxy-2-(di-n-propylamino)tetralin on hippocampal serotonin release and induction of hypothermia in awake rats.[Pubmed:15050424]

Life Sci. 2004 Apr 23;74(23):2865-75.

The effects of (R)- and (S)-optical isomers of 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) and of the racemate (R,S)-8-OH-DPAT on serotonin (5-HT) release in the ventral hippocampus of awake rats and on induction of the whole-body hypothermia were studied. Extracellular 5-HT levels were determined by a newly developed high-sensitive HPLC method based on derivatization with benzylamine and fluorescence detection. The basal levels of 5-HT in 20 min microdialysates from rats perfused with Ringer solution or with Ringer solution containing 1 microM citalopram were 6.3 +/- 1.3 fmol/20 microl and 36.1 +/- 4.2 fmol/20 microl (n=20), respectively. The reduction of hippocampal 5-HT levels induced by subcutaneous (s.c.) administration of (R,S)-8-OH-DPAT (0.3 mg/kg) was significantly attenuated by the presence of 5-HT reuptake inhibitor citalopram in Ringer solution only at its peak value at 40 min (maximal reduction to 60% compared to 46% of control values in Ringer-perfused rats), whereas the overall effects were comparable at both experimental conditions. Injection of (R)-8-OH-DPAT (0.3 mg/kg s.c.) caused further reduction of 5-HT levels, to 49% and 41%, respectively, whereas (S)-8-OH-DPAT (0.3 mg/kg s.c.) caused maximal reduction of 5-HT levels only to 74% of controls in both perfusion groups. Similar pattern and time-courses were observed in rats with hypothermia induced by injection of 8-OH-DPAT enantiomers, where (R,S), (R)-forms were about two-times more potent than the (S)-isomer. It is concluded that the acute systemic dose of (R)-, (S)- and (R,S)-8-OH-DPAT enantiomers exerted enantiomer-specific effects on 5-HT(1A) receptor-mediated function both at the presynaptic and postsynaptic sites as revealed by monitoring hippocampal 5-HT levels and body temperature.

Antagonist activity of meta-chlorophenylpiperazine and partial agonist activity of 8-OH-DPAT at the 5-HT(7) receptor.[Pubmed:10822046]

Eur J Pharmacol. 2000 May 12;396(1):1-8.

This study compared the use of adapter G-proteins to link G(s) coupled G-protein receptors to a Ca(2+) signal, enabling high throughput functional studies using a fluorescent imaging plate reader (FLIPR, Molecular Devices). The pharmacological profile of the human 5-hydroxytryptamine (5-HT(7)) receptor was studied using the adapter G-proteins G(alpha16) and G(qs5) and compared to previously published adenylyl cyclase and receptor binding data. Human embryonic kidney (HEK) 293 cells stably expressing the human 5-HT(7(a)) receptor were transiently transfected with the adapter G-proteins. Changes in intracellular Ca(2+) were monitored using the fluorescent Ca(2+)-indicator Fluo-4.5-Carboxamidotryptamine (5-CT) induced an increase in fluorescence in transfected cells only, which was attenuated by N-ethylmalaeimide and abolished by thapsigargin, consistent with a G-protein mediated mobilisation of intracellular Ca(2+). The pharmacological profile of agonists at the 5-HT(7) receptor was similar using either adapter G-protein. Agonist potency estimates were similar to that reported in binding studies but were greater than that seen in adenylyl cyclase studies. 8-Hydroxy-N, N-dipropylaminotetralin (8-OH-DPAT) and tryptamine acted as partial agonists using the adapter G-proteins, but were full agonists in recombinant systems using adenylyl cyclase. meta-Chlorophenylpiperazine (mCPP) and trifluoro-methylphenyl piperazine (TFMPP) were antagonists on intracellular Ca(2+). Antagonist pharmacological profiles were similar between adapter G-proteins, receptor binding, and adenylyl cyclase studies. These results show that adapter G-proteins can be used to study G(s)-linked receptors using the high throughput FLIPR system measuring changes in intracellular Ca(2+) and provide novel information on mCPP and 8-OH-DPAT.

Alterations of in-vitro 5-HT receptor pharmacology as a function of multiple treatment with 5-hydroxytryptamine or 8-hydroxy-2-(di-N-propylamino) tetralin in rat isolated aorta, uterus and fundus, and guinea-pig isolated trachea.[Pubmed:7897596]

J Pharm Pharmacol. 1994 Nov;46(11):902-5.

The effects of single and multiple (5, 10, or 15 days) administration of the 5-HT1A agonist 8-hydroxy-2-(di-N-propylamino) tetralin (8-OH-DPAT) (3 mg kg-1, i.p.) or 5-HT (3 mg kg-1, i.p.) in-vivo on the response of selected isolated smooth muscles to 5-HT in-vitro were investigated. Single dosing with 8-OH-DPAT did not alter the responses of the isolated tissues (rat aorta, uterus or fundus, or guinea-pig trachea) to 5-HT, while multiple dosing with 8-OH-DPAT produced rightward shifts and a suppression of the maximum response of all these tissues to 5-HT, with the exception of the rat stomach fundus. Multiple administration of 5-HT had no effect on the in-vitro response of the tissues to 5-HT. These data indicate that multiple administration of 8-OH-DPAT desensitizes or down-regulates the peripheral 5-HT2 receptors found on the rat aorta and uterus, and guinea-pig trachea.