 Chemical Structure.png)
Physicochemical Properties
| Molecular Formula | C3H10NO2P |
| Molecular Weight | 122.08286 |
| Exact Mass | 122.037 |
| CAS # | 103680-47-3 |
| PubChem CID | 6335948 |
| Appearance | Typically exists as solid at room temperature |
| Vapour Pressure | 0.001mmHg at 25°C |
| LogP | -1.4 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 3 |
| Rotatable Bond Count | 3 |
| Heavy Atom Count | 7 |
| Complexity | 66 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | NCCCP(=O)O |
| InChi Key | MQIWYGZSHIXQIU-UHFFFAOYSA-O |
| InChi Code | InChI=1S/C3H8NO2P/c4-2-1-3-7(5)6/h1-4H2/p+1 |
| Chemical Name | 3-aminopropyl-hydroxy-oxophosphanium |
| Synonyms | 3-aminopropylphosphinic acid; 103680-47-3; 3-aminopropyl-hydroxy-oxophosphanium; 3-Aminopropanephosphinic acid; (3-aminopropyl)phosphinic acid; CGP-27492; 3-APPA; Cgp 27492; |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | GABAB receptor |
| ln Vitro |
3-Aminopropylphosphinic acid (10 μM) functions as an anti-aging drug for skin[4]. It also induces a concentration-dependent suppression of the cholinergic twitch contraction in the electrically stimulated ileum (IC50=1.84-0.23 μM)[2]. The effects of phosphonic analogues of GABA, beta-alanine and glycine on guinea-pig ileum longitudinal muscle were measured. 3-Aminopropylphosphinic acid (AMPh) and 2-aminoethylphosphonic acid (2-AEPh) were devoid of any effect both in non-stimulated preparations and in electrically-stimulated preparations. The phosphonic analogue of GABA, 3-aminopropylphosphonic acid (3-APPh) possessed a GABAB agonistic effect (relaxation and inhibition of twitch response) at doses of 10(-3)M. No agonistic effect on GABAA receptors was observed. 3-APPh at doses tested (2 X 10(-4)M and 10(-3)M) also displayed antagonistic action on the effects of GABAB agonists producing a parallel shift of the log dose-effect curves of GABA- and (-)-baclofen-inhibition of twitch responses. In contrast 3-APPh did not antagonize the inhibitory effect of morphine and noradrenaline. The contractile effect of GABA, mediated via GABAA receptors, was unaffected by 3-APPh(10(-3)M). It is concluded that 3-APPh is a partial agonist at the GABAB site in guinea-pig ileum. [1] 1. 3-Aminopropylphosphinic acid, a gamma-aminobutyric acid (GABA) analogue, was tested for activity on guinea-pig isolated ileum and rat isolated anococcygeus muscle preparations. The effects of 3-aminopropylphosphinic acid were compared with those of GABA and baclofen. 2. In the electrically stimulated ileum, 3-aminopropylphosphinic acid, like GABA and baclofen, caused a concentration-dependent inhibition of the cholinergic twitch contraction, the IC50 value being 1.84 +/- 0.23 microM (n = 12). Unlike GABA, but like baclofen, 3-aminopropylphosphinic acid did not produce an initial contraction. 3. The inhibitory effects of 3-aminopropylphosphinic acid and baclofen in the guinea-pig ileum were not significantly antagonized by bicuculline (10 microM), phentolamine plus propranolol (both 1 microM), yohimbine (1 microM), naloxone (1 microM), impromidine (1 microM) or 8-phenyltheophylline (10 microM). The inhibitory effects of 3-aminopropylphosphinic acid, but not of baclofen, were however antagonized by phaclofen (500 microM). In addition the effects of 3-aminopropylphosphinic acid were abolished by baclofen desensitization in the guinea-pig ileum. 4. 3-Aminopropylphosphinic acid, GABA and baclofen reduced the twitch contraction evoked by electrical field stimulation in the rat anococcygeus muscle. The IC50 for 3-aminopropylphosphinic acid inhibition of the anococcygeus contraction was 0.89 +/- 0.15 microM (n = 8). 5. It is concluded that 3-aminopropylphosphinic acid is a potent, selective GABAB agonist, being seven times more potent than baclofen in the guinea-pig ileum and five times more potent than baclofen in the rat anococcygues muscle preparations. [2] |
| ln Vivo |
3-Aminopropylphosphinic acid (5 mg/kg; iv) inhibits the guinea pigs' vagal bronchospasm by blocking the actions of GABA[3]. GABA is a known inhibitory neurotransmitter in the CNS. Recent studies have also demonstrated the presence of GABA in peripheral tissue, including lung. To delineate a role for GABA in lung, the effect of GABA and selective GABA agonists and antagonists on neuronally-induced airway contractions in guinea pigs were studied. In vitro, tracheal contractions induced by electrical field stimulation (EFS) were inhibited by tetrodotoxin and atropine indicating that the contractions were mediated by neuronal release of acetylcholine. The contractions caused by EFS, but not those by exogenous acetylcholine, were inhibited by GABA (EC50 = 4.5 microM) and the selective GABA-B agonist baclofen (EC50 = 9 microM), but not by the GABA-A agonist, muscimol. The inhibitory effect of baclofen was not affected by the GABA-A antagonist, bicuculline, but was significantly reversed with the GABA-B antagonists, 3-Aminopropylphosphinic acid (3-APPA) (pA2 = 4.5) and 2-hydroxysaclofen (pA2 = 4.1). In vivo, vagal nerve stimulation (5 V, 20 Hz, 0.5 ms, 5 s) in anesthetized, mechanically ventilated guinea-pigs caused cholinergic-dependent bronchospasms that were inhibited by intravenous GABA (3 and 10 mg/kg) and baclofen (1-10 mg/kg), but not by muscimol. The inhibitory effects of GABA and baclofen against vagal bronchospasm were blocked by 3-APPA (5 mg/kg, i.v.), but not by bicuculline. Responses to the GABA-B agonists were unaltered after the treatment of animals with phentolamine or propranolol to block alpha-adrenergic and beta-adrenergic receptors, respectively. Bronchospasm due to intravenous methacholine was also unchanged by GABA and baclofen [3]. |
| Cell Assay |
‘In vitro’ preparations [1] Experiments were performed in male guinea-pigs (weight range 300-500 g); animals weregUed by a blow on the head; segments ofterminal ileum were quickly removed and placedin a modified Krebs solution of the followingcomposition (mM): KHzP041.3, KCI 3.4, NaCl134.7, CaC12 2.8, MgS04 0.6, NaHC03 16.3,glucose 7.7. Strips of ileal longitudinal musclewith myenteric plexus attached were obtained bythe method of Paton & Zar (1968). Segmentswere mounted in an organ bath, bubbled with amixture of 5% COZ and 95% 02and maintained at37°C. When necessary, electrical stimulation wasperformed following the method described byPaton (1963) and Paton & VLzi (1969). Thestimuli ( 1.5 times maximal rectangular pulses of 1msec duration, at a frequency of 6 per min) were applied using two coaxial platinum electrodesfrom a MARB stimulator. The ileum wasconnected to an isometric transducer under aresting tension of 0.5 g and responses wererecorded on a MARB polygraph. Preparationswere allowed to equilibrate for 60 min beforedrug administration. Drugs were administered ina volume that never exceeded 1% of the total bathvolume (4 ml). The occurrence of desensitization to GABA was prevented by allowing 20 min toelapse between drug administrations. In fact, aswe previously observed (Giotti et al., 1983a;b),both in non-stimulated and in electrically-stimulated preparations, submaximal doses of GABA, repeated at intervals ranging between 15-30 min, evoked the same effects. |
| Animal Protocol |
Animal/Disease Models: guinea pigs[3] Doses: 5 mg/kg Route of Administration: IV Experimental Results: Blocked the inhibitory effects of GABA against vagal broncho-spasm. Guinea-pig ileum [2] Male guinea-pigs (300-450g) were killed by a blow to the head and bled out. Segments of ileum of approximately 3 cm in length were removed from an area 10-15cm proximal to the ileo-caecal junction. Preparations were immediately placed in a modified Krebs solution (BUlbring, 1953) which was continually bubbled with 95% 02 and 5% CO2. Segments were freed of their mesenteric attachment and suspended in 10 ml organ baths containing Krebs solution under an isometric tension of 1 g. Isometric contractions to transmural stimulation (Paton, 1954) were recorded with strain gauge transducers and displayed on an Ormed Multitrace pen recorder. Electrical stimulation of preparations was achieved by passing rectangular pulses (duration 0.5 ms; frequency 0.1 Hz; supramaximal voltage (25-35 V)), from a Grass SD11 stimulator via platinum electrodes. Preparations were allowed to equilibrate for 1 h prior to addition of compounds to the organ bath. Rat anococcygeus [2] Male Wistar rats (200-300 g) were killed by a blow to the head and bled out and their anococcygeus muscles removed as previously described (Gillespie, 1972). The muscles were mounted in organ baths (10 ml) containing modified Krebs solution which was continually gassed with 95% 02 and 5% CO2. A resting tension of 0.5 g was applied and the preparations were field stimulated from Grass SD11 stimulators via platinum ring electrodes with the following stimulus parameters: pulse duration 1 ms; frequency 10 Hz; for 1 s. Isometric muscle responses were measured with a strain gauge transducer and displayed on an Ormed Multitrace pen recorder. Typical tension responses generated in either preparation as a result of electrical stimulation were between 2 and 4 g force. Preparations generating less tension were rejected. In both preparations, sequential agonist concentration-response curves were constructed, allowing 30 min between additions of agonist to minimize tachyphylaxis. When antagonists were used, concentration-response curves to 3-Aminopropylphosphinic acid in the presence of the antagonist were constructed after an initial equiliThe following drugs were used: y-amino-n-butyric acid, (±+baclofen, (±)-propranolol (ICI), phentolamine mesylate, yohimbine hydrochloride, naloxone hydrochloride, 8-phenyltheophylline, impromidine oxylate, bicuculline methiodide, phaclofen and 3-Aminopropylphosphinic acid (prepared by the method of Dingwall et al., 1987a, b). With the exception of 8-phenyltheophylline, all compounds were dissolved in distilled water, subsequent dilutions being made in distilled water and compounds were added to the organ bath in volumes no greater than 1% total volume. 8- Phenyltheophylline was made up in 80% methanol/ 2 M NaOH, subsequent dilutions being made in distilled water and all vehicle controls were negative. Propranolol and phentolamine were added directly to the Krebs solution. |
| References |
[1]. GABA-related activities of amino phosphonic acids on guinea-pig ileum longitudinal muscle. J Auton Pharmacol. 1986 Sep;6(3):163-9. [2]. 3-Aminopropylphosphinic acid--a potent, selective GABAB receptor agonist in the guinea-pig ileum and rat anococcygeus muscle. Br J Pharmacol. 1989 Aug;97(4):1292-6. [3]. Prejunctional GABA-B inhibition of cholinergic, neurally-mediated airway contractions in guinea-pigs. Pulm Pharmacol. 1991;4(4):218-24. [4]. 3-Aminopropyl dihydrogen phosphate (3-APPA; 3-aminopropane phosphoric acid); a novel anti-aging substance. Journal of Investigative Dermatology, vol. 4, no. 106, 2015, p. 895. |
| Additional Infomation |
A bicumlline-insensitive (possibly GABAB)inhibitory effect of 3-APPh on the firing ofcentral neurones has been previously describedby Bioulac, De Tinguy-Moreaud, Vincent &Neuzil, (1979); moreover quite recently Cates,Li, Yakashe, et al., (1984) have demonstratedthat t h i s compound has some aff~tyfor GABAgbinding sites.Regarding GABAA receptors, none of the phosphonic drugs tested showed agonisticactivity on this subtype of receptors: only 3-APPh contracted the ileum but in a bicuculline-and picrotoxin-insensitive manner and thiscontraction was not desensitized by GABA. Thisineffectivenessof 3-APPh on GABAE,receptors isalso in accordance with previous binding studiesperformed at the central level (Galli, Zilletti,Scotton, Adembri & Giotti, 1980; Cates et al.,1984).However our principal interest was in studyingthe antagonistic effect on GABA receptors ofthese drugs: none of them showed an interferencewith the contraction mediated by GABAA,receptors; on the contrary, 3-APPh at high dosesshowed a significant antagonism against GABABmediated inhibitory effects; the antagonist effectof 3-APPh was found to be reversible and specificfor GABA-ergic drugs; 2-AEPh and 3-APPhwere ineffective.A problem that arises is whether the agonisticaction of 3-APPh on GABAB receptors couldinterfere with its antagonistic properties on thesame receptors through a desensitizationphenomenon. The fact that 3-APPh was alsocapable of promptly reversing the GABAA effect on twitch response (Fig. 6)is in favour of a directantagonistic effect. Moreover 3-APPhantagonism of the GABAB effect appeared to becompetitive for the lower dose tested (2 X10- M): dose-effect curves were in a parallelfashion displaced and the maximum effects werepractically unchanged. On the other hand, for thehighest dose (10-3M) the desensitizationphenomenon might play a role; in fact at thisconcentration dose-effect curves were flattenedwhich might be due to the development ofdesensitization.In conclusion, the phosphonic analogue of GABA, 3-Aminopropylphosphinic acid/3-APPh, shows weak GABABantagonistand weak GABAB agonist properties while it isdevoid of any action (agonistic or antagonistic) onGABAA receptors. This profile is probablyinterpretable as that of a partial agonist and isdifferent from that of other drugs suggested asGABAg antagonists: 3-APS (strong GABAAagonist; weak GABAB agonist and antagonist)(Table 2). Therefore it appears that a usefulGABAB antagonist has yet to be found. However,the exact understanding of the differences ofdrugs acting on GABAB receptors may help intheir use as tools in experimental work and indeveloping more selective GABABantagonists.[1] There have been several studies on thi requirements for GABAB receptor acth which it would appear that even minor tions of the baclofen molecule result in total loss of activity (Olpe et al., 1980; Krogsgard-Larsen, 1988). To date, no GABAB agonist has been shown to be more potent than baclofen on the in vitro systems described here. 3-Aminopropylphosphinic acid was found to be seven times more potent than racemic baclofen in the guinea-pig ileum and five times more potent than racemic baclofen in the rat anococcygeus muscle. In studies reported by Dingwall et al. (1987a, b), 3-aminopropylphosphinic acid has been reported to have an affinity for the GABAB receptor 1 10,0 .0 that is twenty times more than the affinity of baclo100 1000 fen. It is interesting to compare the structures and HeTIactivities of the phosphinic analogue of GABA, described here as a potent agonist, to the phosphonic analogue which has been described as a weak partial agonist/antagonist (Luzzi et al., 1986), although the only difference in structure between the two is the acidic moiety. 3-Aminopropylphosphinic acid has a distorted tetrahedral arrangement of atoms around the phosphorus, has only one acidic proton and has the negative charge distributed over two oxygen atoms, thus it is similar in many respects 100 1000 to GABA. While 3-aminopropylphosphoninic acid has a near tetrahedral arrangement of atoms around the phosphorus, has two acidic protons (depending agonists in on pH) and has the negative charge distributed over oeus muscle three oxygen atoms. guinea-pig In the guinea-pig ileum, it would appear that 3- I), baclofen aminopropylphosphinic acid is interacting with were 0.5 ms GABA, receptors located prejunctionally on cholinThe mean ergic terminals. Since 3-aminopropylphosphinic acid Sid was sig- did not cause an initial contraction, it is likely to be s for either devoid of GABAA agonist activity. Although final statistically validation of this assumption awaits a more specific 0 values for and potent GABA5 antagonist, the results with a onse curves number of known specific receptor antagonists Iic acidm(l) suggest that 3-aminopropylphosphinic acid is not mieters were interacting with any other class of receptor. Further, pramaximal tissues desensitised to baclofen, no longer responded 3-amino- to 3-aminopropylphosphinic acid. Clonidine, which ,than mean was employed to test the specificity of the GABAB '<0.05). In receptor desensitization, was equieffective both was signifi- before and during GABAB receptor desensitization. for baclofen Phaclofen has been claimed to be a weak but select least four tive GABAB antagonist (Kerr et al., 1987; Dutar & n shown by Nicholl, 1988). We were able to demonstrate inhibition of the 3-aminopropylphosphinic acid responses in the guinea-pig ileum but not those of baclofen. It is unclear why this should be so, although since phaclofen has more recently been claimed to show GABA, antagonist activity in a variety of test systems (Karlsson et al., 1988; Soltesz et al., 1988), it ve structural does support our hypothesis that 3-aminovation from propylphosphinic acid, is interacting with GABA, r manipula- receptors. [2] The time course of the 3-Aminopropylphosphinic acid response in both the guinea-pig ileum and the rat anococcygeus muscle was similar to that of GABA and baclofen. The response to GABAB agonists in the guinea-pig ileum is commonly observed to be transient in nature while in the rat anococcygeus muscle it is more long-lasting (Bowery et al., 1981; Muhyaddin et al., 1982). Our pharmacological investigations support the claims of Dingwall et al. (1987a, b) that 3- aminopropylphosphinic acid is a highly potent, selective GABAB agonist. Further experiments with this compound may shed light on the physiological role of GABAB receptors in the mammalian intestine.[2] |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| Solubility (In Vivo) |
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 Formulations (e.g. IP/IV/IM/SC) 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). 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 Formulations 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). 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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 8.1913 mL | 40.9567 mL | 81.9135 mL | |
| 5 mM | 1.6383 mL | 8.1913 mL | 16.3827 mL | |
| 10 mM | 0.8191 mL | 4.0957 mL | 8.1913 mL |