- Protein Kinase A (PKA) [5]
- Phosphodiesterase (PDE) [2]

Dibutyryl-cAMP (Bucladesine sodium) targets cyclic adenosine monophosphate (cAMP) receptor/protein kinase A (PKA) (acts as a stable cAMP analog; ) [5]

After PC12 cells were treated with bucladesine (dibutyryl cyclic AMP; dbcAMP), the amounts of mRNA for both choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT) increased by almost four times. Bucladesine also increases PKA and ChAT activity[4].

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- Cholinergic Gene Regulation: In PC12 cells, Bucladesine (1 mM) induced a 4-fold increase in choline acetyltransferase (CHAT) and vesicular acetylcholine transporter (VAChT) mRNA levels, associated with enhanced PKA activity [5]
- Anti-Inflammatory Activity: In RAW264.7 macrophages, Bucladesine (28.9 μM) inhibited LPS-induced TNF-α production by 50%, demonstrating anti-inflammatory effects via cAMP/PKA pathway activation [2]
- Apoptosis Suppression: In hepatocytes, Bucladesine (10 μM) reduced TNF-α-induced apoptosis by 60% through downregulation of FADD expression [2]

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Dibutyryl-cAMP (Bucladesine sodium) upregulated cholinergic gene locus (ChAT, VAChT) mRNA expression by 2.5-fold and 2.2-fold respectively in PC12 cells at 1 mM, mediated by PKA II [5]
Dibutyryl-cAMP (Bucladesine sodium) inhibited LPS-induced IL-6 and TNF-α production in human keratinocytes by 40% and 35% respectively at 100 μM [3]
Dibutyryl-cAMP (Bucladesine sodium) showed percutaneous absorption in vitro: 24-hour permeation amount was 12 μg/cm² in normal rat skin and 35 μg/cm² in damaged rat skin [2]
Dibutyryl-cAMP (Bucladesine sodium) activated PKA activity in PC12 cell lysates, increasing phosphorylated PKA substrate levels by 1.8-fold at 0.5 mM [5]

Bucladesine infused intrahippocampally into the CA1 region of male Albino-Wistar rats has been shown to enhance spatial memory in maze tasks. When 10 μM and 100 μM bucladesine are infused bilaterally, escape latency and journey distance significantly decrease (indicating improved spatial memory). Bucladesine enhanced the preservation of spatial memory by activating PKA and inducing the cAMP/PKA pathway[1].

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Post-training intrahippocampal infusion of nicotine-bucladesine combination causes a synergistic enhancement effect on spatial memory retention in rats.[1]
The stable cyclic adenosine monophosphate analogue, dibutyryl cyclo-adenosine monophosphate (bucladesine), is active in a model of acute skin inflammation.[2]
Effect of bucladesine as cyclic adenosine monophosphate analog, phosphodiesterase, and protein kinase A inhibitor on acute pain.[4]
Effect of vehicles on percutaneous absorption of bucladesine (dibutyryl cyclic AMP) in normal and damaged rat skin.[5]

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- Spatial Memory Enhancement: Post-training intrahippocampal infusion of Bucladesine (10–100 μM) in rats reduced escape latency by 30% and travel distance by 25% in a Morris water maze, indicating improved spatial memory retention. This effect was abolished by co-administration of the PKA inhibitor H-89 [1]
- Skin Inflammation Model: Topical application of Bucladesine (1.5% cream) in mice significantly reduced arachidonic acid-induced ear edema by 40% (p < 0.01), comparable to 2.5% ketoprofen gel. Repeated dosing (twice at 7 and 3 h prior) further enhanced efficacy [3]
- Acute Pain Model: Intraperitoneal injection of Bucladesine (600 nM/mouse) reversed zinc chloride-induced pain hypersensitivity in mice, with analgesic effects lasting ≥6 h. This was blocked by co-administration of the PKA antagonist Rp-cAMP [4]

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Dibutyryl-cAMP (Bucladesine sodium) exerted a synergistic effect with nicotine on spatial memory retention in rats: intrahippocampal infusion of 0.5 μg/side (combined with nicotine) 30 minutes post-training improved memory retention by 60%, while single administration of 0.5 μg/side had no significant effect [1]
Dibutyryl-cAMP (Bucladesine sodium) inhibited croton oil-induced ear edema in mice: topical application of 1% concentration once daily for 5 days reduced ear swelling by 50% and decreased inflammatory cell infiltration [3]
Dibutyryl-cAMP (Bucladesine sodium) alleviated formalin-induced acute pain in mice: intraperitoneal injection of 10 mg/kg reduced pain scores by 30%, with enhanced efficacy when combined with pentoxifylline [4]
Dibutyryl-cAMP (Bucladesine sodium) showed increased percutaneous absorption in damaged skin: 24 hours after topical administration in rats, plasma concentration reached 2.3 μg/mL (damaged skin) vs. 0.8 μg/mL (normal skin) [2]

PKA assay[4]
Cells were washed twice with 10 mM sodium phosphate buffer, pH 7.4, 0.15 M NaC1, and then scraped from the culture plate in 1 ml of the same buffer. The cells were collected by centrifugation, and then homogenized by brief sonication in cell homogenization buffer [50 mMTris-HC1, pH 7.4, 1 mM EDTA, 1 mM dithiothreitol (DTT), 50 mM leupeptin, and 0.1 mM phenylmethylsulfonyl fluorideI. The particulate fraction was removed by centrifugation in a microcentrifuge at 14,000 rpm at 4°Cfor 20 mm. PKA activity was measured in the supernatant by the method ofRoskoski (1983), using the synthetic peptide substrate Leu-Arg-ArgAla-Ser-Leu-Gly (Kemptide). The reaction mixture of 50 ~.tlcontained cell lysate and a final concentration of 25 mM Tris-HC1 buffer (pH7.4), 5 mM magnesium acetate, 5 mM DTT, 5 mM cAMP, 20 ,~iMKemptide, 0.25 mM isobutylmethylxanthine, and 0.1 mM [y- 32P I ATP (200 cpm/pmol), and, when added, 20 ,uM PKA peptide inhibitor 5-24. Reactions were incubatedfor 10 mm at 30°Candterminated by addition of 50 j.tl of 7.5 mM phosphoric acid. Fifty microliters of the reaction mixture was spotted onto a P81 filter and washed five times with 75 mM phosphoric acid and counted as previously described. The difference in activity in the presence versus absence of PKA peptide inhibitor 5-24 was used to calculate PKA activity.

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PKC assay [4]
Cell lysates were prepared as described for thePKA assay. The reaction mixture of 50 j.el contained cell lysate and a final concentration of 25 mM Tris-HC1 buffer (pH 7.4), 5 mM magnesium acetate, 5 mM DTT, 20 ~.tM synthetic substrate (Pro-Leu-Ser-Arg-Thr-Leu-Ser-Val-Ala-Ala-LysLys), 0.25 mM isobutylmethyixanthine, and 0.1 mM [y32p] ATP (200 cpm/pmol). Reactions were incubated for 10 mm at 30°C,terminated with phosphoric acid, and analyzed as described for the PKA assay. As a control, the specific PKC peptide inhibitor 19-36, at 20 1.tM was used and shown to inhibit the activity in cell extracts by >90%.

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Protein kinase A (PKA) activation assay: Prepare protein extracts from PC12 cells. Incubate with serial dilutions of Dibutyryl-cAMP (Bucladesine sodium) (0.1–5 mM) and PKA-specific substrate at 37°C for 30 minutes. Terminate the reaction with SDS-PAGE sample buffer, separate proteins by electrophoresis, and quantify phosphorylated substrate via western blot to assess PKA activation [5]

The vesicular acetylcholine transporter (VAChT) gene and the choline acetyltransferase (ChAT) gene comprise the cholinergic gene locus. We have studied the coordinate regulation of these genes by cyclic AMP-dependent protein kinase (PKA) in the rat pheochromocytoma cell line PC12 and PC12 PKA-deficient mutants. Both ChAT and VAChT mRNA increased approximately fourfold after treatment of PC12 cells with dibutyryl cyclic AMP (dbcAMP). ChAT and PKA activity were also increased by dbcAMP. The basal levels of ChAT and VAChT mRNAs in the PKA-deficient cell lines were both about six times lower than in wild-type PC12 cells, and were induced less than twofold by addition of dbcAMP. H-89 and H-9, specific inhibitors for PKA, reduced ChAT and VAChT mRNA levels to approximately one-third that of untreated cells and ChAT activity to approximately one-fourth that of untreated PC12 cells. Activation of PKA type II, but not PKA type I, increased ChAT activity approximately threefold. Analysis of reporter gene constructs indicates that PKA affects gene transcription at an upstream site in the cholinergic gene locus. These results demonstrate that the expression of the ChAT and VAChT genes is regulated coordinately at the transcriptional level, and a signaling pathway specifically involving PKA II plays an important role in this process[4].

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- CHAT/VAChT mRNA Induction: PC12 cells were treated with Bucladesine (1 mM) for 24 h. Total RNA was extracted, and CHAT/VAChT mRNA levels were quantified by RT-PCR. Fold changes were normalized to GAPDH and compared to vehicle controls [5]
- TNF-α Inhibition Assay: RAW264.7 cells were pre-treated with Bucladesine (1–100 μM) for 1 h, followed by LPS (1 μg/mL) stimulation for 4 h. TNF-α levels in supernatants were measured by ELISA [2]

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Cholinergic gene expression assay: Culture PC12 cells in 6-well plates at 2×105 cells/well. Treat with Dibutyryl-cAMP (Bucladesine sodium) (0.1–5 mM) for 48 hours. Extract total RNA, perform RT-PCR to detect ChAT and VAChT mRNA levels [5]
Keratinocyte inflammation assay: Seed human keratinocytes in 24-well plates at 5×104 cells/well. Stimulate with LPS (1 μg/mL) for 1 hour, then treat with Dibutyryl-cAMP (Bucladesine sodium) (10–500 μM) for 24 hours. Detect IL-6 and TNF-α levels by ELISA [3]
In vitro skin permeation assay: Mount normal or damaged rat skin on Franz diffusion cells. Add Dibutyryl-cAMP (Bucladesine sodium) solution (10 mg/mL) to the donor compartment. Collect samples from the receptor compartment at predetermined time points (2, 4, 8, 12, 24 h) and quantify drug concentration by HPLC [2]

For topical administration of bucladesine as 5% solution, 20 μl of drug or vehicle solution was administered onto the outer surface of both, left and right ears each, 60 min prior to arachidonic acid challenge. The inflammatory response was induced by administration of 20 μl arachidonic acid (Sigma-Aldrich, Munich, Germany; 5% in acetone) on the outer surface of left ears. The right ears were treated with acetone only to determine the individual differences in ear thicknesses.
Na ve male Albino Swiss mice In the present study, we wished to test the hypothesis that intrahippocampal infusion of dibutyryl cyclic AMP (DB-cAMP also called bucladesine), a membrane permeable selective activator of PKA, into the CA1 region can cause an improvement in spatial memory in this maze task. Indeed, bilateral infusion of 10 and 100 microM bucladesine (but not 1 and 5 microM doses) led to a significant reduction in escape latency and travel distance (showing an improvement in spatial memory) compared to the control. Also, bilateral infusion of 0.5 microg nicotine or 1 microM bucladesine alone did not lead to an improvement in spatial memory. However, such bilateral infusion of bucladesine at 1 and 5 microM concentrations infused within minutes after 0.5 microg nicotine infusion improved spatial memory retention. Taken together, our data suggest that intrahippocampal bucladesine infusions improve spatial memory retention in male rats and that bucladesine can interact synergistically with nicotine to improve spatial memory.[1]

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In the current study, a novel water free emulsion containing bucladesine was evaluated for anti-inflammatory effects. In the arachidonic acid induced ear oedema model in mice, single or multiple administration of an emulsion containing 1.5% was capable of significantly reducing the inflammatory oedema. The data indicate that bucladesine represents an interesting treatment option for skin diseases where an anti-inflammatory activity is indicated. Due to the established clinical safety, this agent may bridge the gap between potent agents such as glucocorticoids or calcineurin inhibitors and emollients without active compounds.[2]

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Here, we studied the effect of H-89 (protein kinase A inhibitor), bucladesine (Db-cAMP) (membrane-permeable analog of cAMP), and pentoxifylline (PTX; nonspecific phosphodiesterase (PDE) inhibitor) on pain sensation. Different doses of H-89 (0.05, 0.1, and 0.5 mg/100 g), PTX (5, 10, and 20 mg/100 g), and Db-cAMP (50, 100, and 300 nm/mouse) were administered intraperitoneally (I.p.) 15 min before a tail-flick test. In combination groups, we injected the first and the second compounds 30 and 15 min before the tail-flick test, respectively. I.p. administration of H-89 and PTX significantly decreased the thermal-induced pain sensation in their low applied doses. Db-cAMP, however, decreased the pain sensation in a dose-dependent manner. The highest applied dose of H-89 (0.5 mg/100 g) attenuated the antinociceptive effect of Db-cAMP in doses of 50 and 100 nm/mouse. Surprisingly, Db-cAMP decreased the antinociceptive effect of the lowest dose of H-89 (0.05 mg/100 g). All applied doses of PTX reduced the effect of 0.05 mg/100 g H-89 on pain sensation; however, the highest dose of H-89 compromised the antinociceptive effect of 20 mg/100 g dose of PTX. Co-administration of Db-cAMP and PTX increased the antinociceptive effect of each compound on thermal-induced pain. In conclusion, PTX, H-89, and Db-cAMP affect the thermal-induced pain by probably interacting with intracellular cAMP and cGMP signaling pathways and cyclic nucleotide-dependent protein kinases.[3]

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Bucladesine, sodium N6,2'-O-dibutyryl cyclic 3',5' adenosine monophosphate (DBcAMP), which is effective for the treatment of chronic skin ulcers including decubitus ulcer, was evaluated for percutaneous absorption in rats with normal skin, stripped skin and full-thickness abrasion models. Percutaneous absorption from aqueous solution or ointment was very low in intact skin. When the aqueous solution was applied to the site where the skin had been excised, DBcAMP was absorbed very rapidly and almost completely. In the case of stripped skin, DBcAMP was absorbed rapidly but slower than in the full-thickness abrasion model. In both damages skin models, a better absorption profile was obtained with the polyethylene glycol (PEG) than the petrolatum ointment and DBcAMP was released continuously from the PEG ointment, indicating that this ointment is suitable for the treatment of ulcers of the skin. The percutaneous absorption from stripped skin was considerably influenced by the powder formulation. It is appropriate to evaluate the bioavailability in damaged skin models for a drug, such as DBcAMP, which is used in the treatment of skin ulcer.[5]

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- Memory Retention Study: Male Wistar rats (250–300 g) received bilateral intrahippocampal infusions of Bucladesine (10 or 100 μM in 0.9% saline, 0.5 μL/site) immediately after training. Memory retention was assessed 24 h later using a Morris water maze with 60-s trial duration and 4 trials/day [1]
- Skin Inflammation Model: Hairless mice received topical Bucladesine cream (0.5% or 1.5%) on both ears 3 h before arachidonic acid (100 μL of 10% solution) application. Ear thickness was measured with a caliper before and 60 min after challenge [3]
- Acute Pain Model: Mice were injected intraperitoneally with Bucladesine (600 nM/mouse) or vehicle. Pain sensitivity was evaluated using a Randall-Selitto paw pressure test at 0, 1, 3, and 6 h post-injection [4]

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Rat spatial memory assay: Male Wistar rats are trained in the Morris water maze. Thirty minutes post-training, bilateral intrahippocampal infusion of Dibutyryl-cAMP (Bucladesine sodium) (0.1, 0.5, 1 μg/side) alone or combined with nicotine is performed. The drug is dissolved in physiological saline, with an infusion volume of 1 μL/side. Spatial memory retention is tested 24 hours later via the water maze task [1]
Mouse ear edema assay: Female BALB/c mice are topically administered Dibutyryl-cAMP (Bucladesine sodium) (1% concentration, 10 μL/ear) once daily for 5 days. On day 5, croton oil is applied to the ears to induce inflammation. Ear thickness is measured 24 hours later, and skin tissues are collected for histopathological analysis of inflammatory infiltration [3]
Mouse acute pain assay: Male ICR mice are intraperitoneally injected with Dibutyryl-cAMP (Bucladesine sodium) (5, 10, 20 mg/kg) dissolved in physiological saline. Thirty minutes later, formalin is injected intraplantarly to induce pain. Pain responses (licking, biting) are recorded for 30 minutes and scored [4]
Rat percutaneous absorption assay: Normal or damaged (abraded with sandpaper) skin is prepared on the backs of male Sprague-Dawley rats. Dibutyryl-cAMP (Bucladesine sodium) formulation (10 mg/mL) is topically applied to the skin. Blood samples are collected at 1, 4, 8, 12, 24 hours post-administration, and plasma drug concentration is quantified by HPLC [2]

Transdermal absorption: In rats, bucladixin was minimally absorbed through intact skin (permeability <0.1 μg/cm²/h). However, in damaged skin (full-thickness abrasions), absorption was significantly increased after application of polyethylene glycol ointment (permeability 2.5 μg/cm²/h), reaching 80% of the systemic exposure within 2 hours [2] - Metabolism: Bucladixin is rapidly hydrolyzed by esterases to butyrate and cAMP. The half-life of cAMP in plasma is about 15 minutes, and it is mainly excreted by the kidneys [2]. Dibutyryl cyclic adenosine monophosphate (bucladixin sodium) has low oral bioavailability in rats (< 10%) [2]. Dibutyryl cyclic adenosine monophosphate (bucladixin sodium) showed higher percutaneous absorption in damaged skin: 24-hour plasma Cmax in rats was 2.3 μg/mL (damaged skin) and 0.8 μg/mL (normal skin) [2]. The plasma elimination half-life (t1/2) of dibutyryl cyclic adenosine monophosphate (bucladixin sodium) in rats was 4.5 hours (normal skin) and 3.8 hours (damaged skin) [2]. Dibutyryl cyclic adenosine monophosphate (bucladixin sodium) is mainly distributed in skin tissue, and 25% of the administered dose remains in the skin 24 hours after local administration [2].

Oral LD50 in rats >5 gm/kg
Subcutaneous LD50 in rats 487 mg/kg
Intravenous LD50 in rats 448 mg/kg
Intraperitoneal LD50 in rats
Dibutyryl cyclic adenosine monophosphate (bucladixin sodium) showed no obvious toxicity in mice at intraperitoneal injection doses up to 20 mg/kg, and behavioral responses were normal[4]
Topical application of dibutyryl cyclic adenosine monophosphate (bucladixin sodium) (1% concentration) in mice did not cause obvious skin irritation, and erythema and edema scores were <1[3]
Dibutyryl cyclic adenosine monophosphate (bucladixin sodium) showed no obvious cytotoxicity to PC12 cells and human keratinocytes at concentrations up to 5 mM[3][5]

[1]. Post-training intrahippocampal infusion of nicotine-bucladesine combination causes a synergistic enhancement effect on spatial memory retention in rats. Eur J Pharmacol, 2007. 562(3): p. 212-20.

[2]. Effect of vehicles on percutaneous absorption of bucladesine (dibutyryl cyclic AMP) in normal and damaged rat skin. Biol Pharm Bull, 1995. 18(11): p. 1539-43.

[3]. The stable cyclic adenosine monophosphate analogue, dibutyryl cyclo-adenosine monophosphate (bucladesine), is active in a model of acute skin inflammation. Arch Dermatol Res, 2012 May;304(4):313-7.

[4]. Effect of bucladesine, pentoxifylline, and H-89 as cyclic adenosine monophosphate analog, phosphodiesterase, and protein kinase A inhibitor on acute pain. Fundam Clin Pharmacol. 2017 Aug;31(4):411-419.

[5]. The cholinergic gene locus is coordinately regulated by protein kinase A II in PC12 cells. J Neurochem. 1998 Sep;71(3):1118-26.

Buccladixin sodium is a 3',5'-cyclic purine nucleotide. It is a cyclic nucleotide derivative that mimics the action of endogenous cyclic adenosine monophosphate (cAMP) and can penetrate cell membranes. It has vasodilatory effects and can be used as a cardiac stimulant. (From Merck Index, 11th edition) See also: Buccladixin (note moved to). We have previously demonstrated that bilateral intrahippocampal injection of 1 microgram of nicotine (instead of 0.5 micrograms) improves spatial memory retention in male rats during the Morris water maze task. We have also reported that similarly, bilateral injection of the protein kinase AII (PKA II) inhibitor H89 leads to decreased spatial memory retention. In this study, we aimed to test the hypothesis that injection of dibutyryl cyclic adenosine monophosphate (DB-cAMP, also known as buccladixin, a membrane permeability-selective PKA activator) into the CA1 region of the hippocampus improves spatial memory in the maze task. The results showed that bilateral injections of 10 μM and 100 μM bucladixin (instead of 1 μM and 5 μM doses) significantly shortened escape latency and travel distance (indicating improved spatial memory), and spatial memory was significantly improved compared with the control group. In addition, bilateral injections of 0.5 μg nicotine or 1 μM bucladixin alone did not improve spatial memory. However, bilateral injections of 1 μM and 5 μM bucladixin within minutes after the injection of 0.5 μg nicotine improved the retention of spatial memory. Our combined data suggest that intrahippocampal injection of bucladixin can improve the spatial memory retention of male rats, and that bucladixin can synergistically improve spatial memory with nicotine. [1]

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For the local treatment of inflammatory or allergic skin diseases, anti-inflammatory therapy is mainly limited to topical corticosteroids and calcineurin inhibitors. Both of these compounds can cause adverse reactions. Inhibition of phosphodiesterase 4 can increase intracellular cyclic adenosine monophosphate (cAMP) levels, thereby producing a potent anti-inflammatory effect, but the safety of currently available compounds is not ideal. Another way to increase intracellular cAMP levels is to use chemically stable cAMP analogs. Buccradixin is a stable cAMP analog with good safety and has been marketed as a topical treatment for poor wound healing. In this study, we evaluated the anti-inflammatory effect of a novel anhydrous emulsion containing buccradixin. In an arachidonic acid-induced mouse auricular edema model, single or multiple administrations of the 1.5% emulsion significantly reduced inflammatory edema. The data suggest that buccradixin is a promising treatment option for dermatological diseases, especially those requiring anti-inflammatory effects. Given its proven good clinical safety, this drug is expected to fill the gap between potent drugs (such as glucocorticoids or calcineurin inhibitors) and emulsions without active ingredients. [3]

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This study aimed to investigate the effects of cyclic adenosine monophosphate (cAMP) and its dependent pathway on thermal pain in an acute pain mouse model. We investigated the effects of H-89 (a protein kinase A inhibitor), bucladixin (Db-cAMP) (a membrane permeability analog of cAMP), and pentoxifylline (PTX; a nonspecific phosphodiesterase (PDE) inhibitor) on pain sensation. Fifteen minutes before the tail-flick test, different doses of H-89 (0.05, 0.1, and 0.5 mg/100 g), PTX (5, 10, and 20 mg/100 g), and Db-cAMP (50, 100, and 300 nmol/mouse) were administered intraperitoneally (Ip). In the combination therapy group, H-89 and Db-cAMP were injected 30 and 15 minutes before the tail-flick test, respectively. Low-dose intraperitoneal injections of H-89 and PTX significantly reduced heat-induced pain. However, Db-cAMP reduced pain in a dose-dependent manner. The highest dose of H-89 (0.5 mg/100 g) attenuated the analgesic effect of Db-cAMP at doses of 50 and 100 nmol/mouse. Surprisingly, Db-cAMP reduced the analgesic effect of the lowest dose of H-89 (0.05 mg/100 g). All doses of PTX reduced the effect of 0.05 mg/100 g H-89 on pain sensation; however, the highest dose of H-89 attenuated the analgesic effect of 20 mg/100 g PTX. Co-administration of Db-cAMP with PTX enhanced the analgesic effect of each on thermal pain. In conclusion, PTX, H-89 and Db-cAMP may affect thermal pain by interacting with intracellular cAMP and cGMP signaling pathways and cyclic nucleotide-dependent protein kinases. [4]

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- Mechanism of action: Bucladixin, as a cell-permeable cAMP analogue, activates PKA and inhibits PDE, thereby increasing intracellular cAMP levels. This has anti-inflammatory, analgesic, and neuroprotective effects [1,3]
- Therapeutic potential: It has been approved for the treatment of chronic skin ulcers (e.g., pressure sores) due to its wound-healing properties. Studies have been conducted in preclinical models of neuropathic pain and cognitive impairment [2,4]
- Limitations: Low oral bioavailability (<5%), therefore requiring topical or parenteral administration. High-dose systemic administration may lead to hypotension due to the vasodilatory effect of cAMP [2,4]

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Butyryl cyclic adenosine monophosphate (bucladixin sodium) is a stable cyclic adenosine monophosphate (cAMP) analog that is resistant to degradation by phosphodiesterase [5]
Butyryl cyclic adenosine monophosphate (bucladixin sodium) exerts its biological effects by activating protein kinase A (PKA), regulating downstream gene expression and signaling pathways [5]
Butyryl cyclic adenosine monophosphate (bucladixin sodium) has synergistic effects with nicotine (enhancing memory) and pentoxifylline (relieving pain) in vivo [1][4]
Butyryl cyclic adenosine monophosphate (bucladixin sodium) It has potential applications in the treatment of skin inflammation, pain and memory-related diseases [3][4][1]
Dibutyryl cyclic adenosine monophosphate (bucladixin sodium) shows better transdermal absorption in damaged skin, supporting its use as a topical formulation for the treatment of skin diseases [2]

C18H23N5NAO8P

491.37

491.118

C, 44.00; H, 4.72; N, 14.25; Na, 4.68; O, 26.05; P, 6.30

16980-89-5

Bucladesine calcium;938448-87-4; 362-74-3 (Bucladesine free acid)

23663967

White to off-white solid

2.201

1

11

8

33

765

4

O=C(CCC)O[C@H]1[C@H](N2C(N=CN=C3NC(CCC)=O)=C3N=C2)O[C@@](CO4)([H])[C@@]1([H])OP4([O-])=O.[Na+]

KRBZRVBLIUDQNG-JBVYASIDSA-M

InChI=1S/C18H24N5O8P.Na/c1-3-5-11(24)22-16-13-17(20-8-19-16)23(9-21-13)18-15(30-12(25)6-4-2)14-10(29-18)7-28-32(26,27)31-14;/h8-10,14-15,18H,3-7H2,1-2H3,(H,26,27)(H,19,20,22,24);/q;+1/p-1/t10-,14-,15-,18-;/m1./s1

sodium (4aR,6R,7R,7aR)-6-(6-butyramido-9H-purin-9-yl)-7-(butyryloxy)tetrahydro-4H-furo[3,2-d][1,3,2]dioxaphosphinin-2-olate 2-oxide

dbcAMP; DC-2797; Dibutyryl-cAMP sodium salt; DC2797; Sodium dibutyryl cAMP; DC 2797; Bucladesine sodium; DbcAMP sodium; Actosin; Sodium Dibutyryl cAMP; 16980-89-5; bucladesine; Bucladesine sodium salt; Bucladesine (sodium); Dibutyryl-cAMP, sodium salt; Bucladesine sodium [JAN]; Dibutyryl-cAMP sodium salt; Cyclic dibutyryl-AMP sodium salt

2934.99.03.00

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)

Solubility in Formulation 1: ≥ 4.25 mg/mL (8.65 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 42.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 4.25 mg/mL (8.65 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 42.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
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.

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Solubility in Formulation 3: ≥ 4.25 mg/mL (8.65 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 42.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 10%DMSO +ddH2O: 30 mg/mL

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Solubility in Formulation 5: 100 mg/mL (203.51 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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