5-HT1A Receptor ( pIC50 = 8.19 ); 5-HT7 Receptor ( pIC50 = 466 nM )

At doses less than 100 nM, 8-OH-DPAT hydrobromide (8-Hydroxy-DPAT) has no effect on 5-HT1B binding [1].

---

In vitro activity: The medication only shows a slight improvement in the 5-HT1B subtype; 5.42 ± 0.08 (n = 5) is the pIC50. Because 8-OH-DPAT does not affect 5-HT1B binding at concentrations below 100 nM[1]. In cultured human RPE cells, 8-OH-DPAT can lower oxidative damage, boost antioxidant defense, and decrease the accumulation of lipofuscin derived from both autophagic and photoreceptor outer segment sources[4].

In animals exposed to 3,4-methylenedimethamphetamine (MDMA), the highest doses of 8-OH-DPAT hydrobromide (8-Hydroxy-DPAT) hydrobromide (32, 56, 80, and 100 mg/kg; surgical injection; 15 minutes before testing) significantly interfered with sustained focus and Reinforcing effect (gradual entry range; PR), but not in control animals [1].

---

The selective 5-HT1A-receptor agonist 8-OH DPAT, when injected intravenously, quickly and with little variability reverses the bradycardic and hypotensive responses that are established during severe bleeding. The blood-brain barrier can be easily crossed by 8-OH-DPAT because it is comparatively lipophilic[3].

---

Central administration of serotonergic 5-HT1A receptor agonists delays the reflex sympatholytic response to severe hemorrhage in conscious rats. To determine the region where 5-HT1A receptor agonists act to mediate this response, recovery of mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) was compared in hemorrhaged rats after injection of the selective 5-HT1A agonist, (+)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH DPAT), in various regions of the cerebroventricular system or the systemic circulation. Three minutes after injection of 8-OH-DPAT (48 nmol/kg), MAP and RSNA were higher in hemorrhaged rats given drug in the fourth ventricle (94 +/- 5 mmHg, 82 +/- 18% of baseline) or the systemic circulation (90 +/- 4 mmHg, 113 +/- 15% of baseline) than in rats given drug in the Aqueduct of Sylvius (63 +/- 4 mmHg, 27 +/- 11% of baseline), the lateral ventricle (42 +/- 3 mmHg, -8 +/- 18% of baseline), or in rats given saline in various brain regions (47 +/- 5 mmHg, -42 +/- 10% of baseline). A lower-dose injection of 8-OH DPAT (10 nmol/kg) also accelerated the recovery of MAP and RSNA in hemorrhaged rats when given in the fourth ventricle (94 +/- 26 mmHg, 72 +/- 33% of baseline 3 min after injection) but not the systemic circulation (46 +/- 4 mmHg, -25 +/- 30% of baseline). These data indicate that 8-OH DPAT acts on receptors in the hindbrain to reverse the sympatholytic response to hemorrhage in conscious rats. [3]

---

5-HT1A agonist 8-OH DPAT mediates neuroprotection in a mouse model of AMD. 5-HT1A agonist 8-OH DPAT reduces lipofuscin accumulation in vivo. [4]

8-OH-DPAT (also known as 8-Hydroxy-DPAT) is a well-established, strong, and specific 5-HT1A agonist, with a pIC50 of 8.19. 8-OH-DPAT weakly binds to 5-HT1B with pIC50 of 5.42 and pIC50 <5 for 5-HT; it has a selectivity of almost a thousand times for a subtype of the 5-HT1 binding site and a Ki of 466 nM for 5-HT7. Furthermore In cultured human RPE cells, it can decrease oxidative damage, boost antioxidant defense, and lessen the accumulation of lipofuscin produced by both autophagy and photoreceptor outer segment. In orexin-KO mice, narcoleptic-like sleep dysfunction is caused by 5-HT1A receptor dysfunction, which may also contribute to orexin deficiency-induced sleep disorders. In addition, the use of 5-HT1A receptor agonists like 8-OH-DPAT may be helpful in treating sleep disorders caused by orexin deficiencies.

Cells are exposed to H2O2 (200 µM) for 1 hour and either pre-or post treated with 8-OH DPAT (10 µM) for 24 hours. All measurements for the pretreatment phase are taken 24 hours after the H2O2 exposure, and for the posttreatment phase, 8-OH DPAT is added right away. Management of 5HT1A agonists: Addition of 8-OH DPAT, a 5-HT1A receptor agonist, to the culture medium at concentrations ranging from 0.1 to 20 µM is done every 48 hours to evaluate the compound's capacity to inhibit lipofuscin formation in cultured stem cells. PBS-only-receiving cells served as negative controls in all experiments, which were conducted in basal medium. In order to find out if the effects of 8-OH DPAT persist after 5-HT1A receptor agonist treatment is stopped, the cells are kept in basal medium or fed POS for an additional 28 days after the 8-OH DPAT treatment is stopped. In order to determine whether 8-OH DPAT can eliminate lipofuscin that has already been present, autophagy- and phagocytic-derived lipofuscin are allowed to build up as previously mentioned, and then 8-OH DPAT is added every two days for a maximum of 28 days. We include the 5-HT1A receptor antagonist S(-)-UH-301 at 5 µM in some experiments to verify that 8-OH DPAT is acting through the 5-HT1A receptor agonist. In order to ascertain how the timing of 8-OH DPAT treatment affects oxidative stress markers, RPE cultures are either treated with the 5HT1A agonist for 3 or 24 hours following exposure to H2O2 or pre-treated with 8-OH DPAT (at 1 or 10 µM) for 3 or 24 hours prior to exposure to 200 µM H2O2 for 1 hour. As a negative control, cells that are not subjected to an oxidative stressor are used, and as a positive control, cells that are subjected to an oxidative stressor but do not receive 8-OH DPAT. The only function of cells exposed to 8-OH DPAT is that of an extra control.

Mice: An infrared sensor installed in each mouse's home cage monitors the animals' locomotor activity. Locomotor activity is recorded at 30-min intervals beginning at 8:00 a.m. and 8:00 p.m., respectively, to compare the activity during the light and dark periods. All medications are given at 8:00 p.m., and locomotor activity is then monitored for three hours to determine the effects of psychostimulants (8-OH-DPAT, 1, 3 mg/kg, s.c., etc.) on this activity during the dark period.

---

Experimental Design [2]
Before the experiment, the animals were connected to the recording instrumentation and a withdrawal pump while resting unrestrained in their home cage. The injector containing drug for brain injection was filled with appropriate fluid and placed in the guide cannula before habituation. The rat was then allowed to rest undisturbed for at least 2 h before hemorrhage. Arterial pressure, HR, and RSNA were recorded continuously beginning 10 min before the hemorrhage and ending 20 min after hemorrhage termination. Controlled blood withdrawal was initiated at a rate of 3.2 ml · min−1 · kg−1for 6 min, after which the speed was reduced to 0.53 ml/min for an additional 4 min. In preliminary tests, this procedure was found to produce a consistent fall in MAP, HR, and RSNA after withdrawal of ∼11.2 ml/kg blood or ∼14% of estimated blood volume. The subsequent change to the lower rate of withdrawal was sufficient to maintain bradycardic and sympatholytic responses until hemorrhage termination. [2]
After the initiation of blood withdrawal (7 min), 48 nmol/kg 8-OH DPAT (in 0.5 μl saline) or an equivalent volume of saline was injected over 20 s in either the lateral ventricle, the Aqueduct of Sylvius, or the fourth ventricle. In a fourth group, drug or vehicle was injected intravenously in a volume of 5 μl and flushed with an additional 100 μl of saline over 20 s. All injections were made remotely via tubing that extended outside the cage. After drug injection, no further intervention or resuscitation was performed before termination of the experiment. The dose of 8-OH DPAT chosen for use in these initial studies corresponded to the ED50determined in prior experiments to increase the volume of blood withdrawal that produced a 40-mmHg fall in blood pressure when injected in the lateral ventricle 15 min before hemorrhage. In a separate set of experiments, responses to a lower dose (10 nmol/kg) injection of 8-OH DPAT in the fourth ventricle or systemic was assessed after hemorrhage in the same manner. An additional sham-hemorrhage group, instrumented in the same manner, was injected with 10 nmol/kg 8-OH-DPAT in the fourth ventricle without prior hemorrhage.[2]
After termination of the experiment, rats were killed with an overdose of pentobarbital sodium (100 mg/kg iv). Cannulated rats were subsequently given intercerebroventricular injections of 0.5 μl toliudine blue (0.5%). The brains were removed quickly and postfixed in 10% formalin overnight. The brains were cut the following day to confirm proper cannula placement. Only data from animals in which dye was found to have diffused through the ventricular system (i.e., dye was not injected in tissue) were included in the data analysis.

---

Effect of 8-OH DPAT in the SOD2 knockdown model for AMD [4]
Mice were randomly assigned to one of three groups and received daily subcutaneous injections of either sterile saline, 0.5 mg/kg body weight 8-OH DPAT in sterile saline (low dose), or 5.0 mg/kg 8-OH DPAT (high dose). At monthly intervals mice were evaluated by digital fundus imaging, full-field scotopic (dark adapted) electroretinography (ERG) and spectral domain optical coherence tomography (SD-OCT). At four months, mice were euthanized and eyes were prepared for cryosectioning. Confocal microscroscopy was used to measure autofluorescence in the RPE layer of untreated eyes and virus-treated eyes with or without 8-OH DPAT. Excitation frequency was 387 nm and emission frequency was 440–684 nm and fluorescence intensity was assessed using ImageJ. Sections were also used to assess damage to retinal structure by light microscopy and immunostaining for 8-Oxo-2′-deoxyguanosine (8OHdG) (Abcam, Cambridge, MA, USA) as a measurement of oxidative stress using previously described methodology

[1]. 8-Hydroxy-2-(di-n-propylamino)-tetralin discriminates between subtypes of the 5-HT1 recognition site. Eur J Pharmacol. 1983 May 20;90(1):151-3.

[2]. 5-HT1A agonists and dopamine: the effects of 8-OH-DPAT and buspirone on brain-stimulation reward. J Neural Transm Gen Sect. 1991;83(1-2):139-48.

[3]. 5-HT1A receptor agonist 8-OH-DPAT acts in the hindbrain to reverse the sympatholytic response to severe hemorrhage. Am J Physiol Regul Integr Comp Physiol. 2003 Mar;284(3):R782-91.

[4]. The 5HT1a receptor agonist 8-Oh DPAT induces protection from lipofuscin accumulation and oxidative stress in the retinal pigment epithelium. PLoS One. 2012;7(4):e34468.

[5]. Cognitive performance of MDMA-treated rhesus monkeys: sensitivity to serotonergic challenge. Neuropsychopharmacology. 2002 Dec;27(6):993-1005.

A serotonin 1A-receptor agonist that is used experimentally to test the effects of serotonin.
8-OH-DPAT is a tetralin substituted at positions 1 and 7 by hydroxy and dipropylamino groups respectively It has a role as a serotonergic antagonist. It is a member of tetralins, a member of phenols and a tertiary amino compound. It derives from a hydride of a tetralin.
A serotonin 1A-receptor agonist that is used experimentally to test the effects of serotonin.

---

Two specific 5-HT1A agonists, 8-OH-DPAT (0-300 micrograms/kg), and buspirone (0-3.0 mg/kg), were tested on variable-interval, threshold-current self-stimulation of rat lateral hypothalamus. Buspirone produced a prolonged monotonic depression of responding, whereas the effects of 8-OH-DPAT were biphasic: 3.0 micrograms/kg produced a sustained enhancement of responding while higher doses (100-300 micrograms/kg) produced a relatively short-lasting depression. This biphasic pattern parallels previously reported effects of 8-OH-DPAT on food intake and on various other behaviours. Threshold-current self-stimulation is highly sensitive to alterations in dopaminergic transmission but relatively insensitive to changes in 5-HT. Thus the facilitatory effect of low-dose 8-OH-DPAT seems most plausibly interpreted in terms of enhanced dopaminergic transmission. This could be brought about by 5HT1A autoreceptor-mediated inhibiton of 5-HT release and consequent disinhibition of dopaminergic transmission. Depression of self-stimulation by higher doses of 8-OH-DPAT may reflect the activity of 8-OH-DPAT at postsynaptic 5-HT receptors, with consequent inhibition of DA transmission. Suppression of responding after buspirone at all doses tested may reflect the action of this compound as a partial agonist at postsynaptic 5-HT receptors, and/or its effects on other systems. [2]

---

Age-related macular degeneration (AMD), a major cause of blindness in the elderly, is associated with oxidative stress, lipofuscin accumulation and retinal degeneration. The aim of this study was to determine if a 5-HT(1A) receptor agonist can reduce lipofuscin accumulation, reduce oxidative damage and prevent retinal cell loss both in vitro and in vivo. Autophagy-derived and photoreceptor outer segment (POS)-derived lipofuscin formation was assessed using FACS analysis and confocal microscopy in cultured retinal pigment epithelial (RPE) cells in the presence or absence of the 5-HT(1A) receptor agonist, 8-OH DPAT. 8-OH DPAT treatment resulted in a dose-dependent reduction in both autophagy- and POS-derived lipofuscin compared to control. Reduction in autophagy-induced lipofuscin was sustained for 4 weeks following removal of the drug. The ability of 8-OH DPAT to reduce oxidative damage following exposure to 200 µM H(2)O(2) was assessed. 8-OH DPAT reduced superoxide generation and increased mitochondrial superoxide dismutase (MnSOD) levels and the ratio of reduced glutathione to the oxidized form of glutathione in H(2)O(2)-treated cells compared to controls and protected against H(2)O(2)-initiated lipid peroxidation, nitrotyrosine levels and mitochondrial damage. SOD2 knockdown mice, which have an AMD-like phenotype, received daily subcutaneous injections of either saline, 0.5 or 5.0 mg/kg 8-OH DPAT and were evaluated at monthly intervals. Systemic administration of 8-OH DPAT improved the electroretinogram response in SOD2 knockdown eyes of mice compared to knockdown eyes receiving vehicle control. There was a significant increase in the ONL thickness in mice treated with 8-OH DPAT at 4 months past the time of MnSOD knockdown compared to untreated controls together with a 60% reduction in RPE lipofuscin. The data indicate that 5-HT(1A) agonists can reduce lipofuscin accumulation and protect the retina from oxidative damage and mitochondrial dysfunction. 5-HT(1A) receptor agonists may have potential as therapeutic agents in the treatment of retinal degenerative disease.[4]

C16H26BRNO

328.2877

327.12

C, 58.54; H, 7.98; Br, 24.34; N, 4.27; O, 4.87

76135-31-4

8-OH-DPAT;78950-78-4; 76135-31-4 (HBr); 141215-27-2 (HCl)

6917794

White to off-white solid powder

4.329

2

2

5

19

237

0

BATPBOZTBNNDLN-UHFFFAOYSA-N

InChI=1S/C16H25NO.BrH/c1-3-10-17(11-4-2)14-9-8-13-6-5-7-16(18)15(13)12-14;/h5-7,14,18H,3-4,8-12H2,1-2H3;1H

7-(dipropylamino)-5,6,7,8-tetrahydronaphthalen-1-ol;hydrobromide

76135-31-4; 8-Hydroxy-DPAT hydrobromide; 8-OH-DPAT HRr; 8-Hydroxy-2-dipropylaminotetralin hydrobromide; 8-OH-dpat hydrobromide; 87394-87-4; UNII-G8TFV2F5CP; G8TFV2F5CP;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~25 mg/mL (~76.15 mM)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

---

Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

View More

Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

---

Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

View More

Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

---

Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

---

 (Please use freshly prepared in vivo formulations for optimal results.)