| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
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| 50mg |
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| Other Sizes |
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| Targets |
AChR; natural pyridine alkaloid from Areca triandra
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| ln Vitro |
A series of tertiary and quaternary N-substituted guvacine (1,2,5,6-tetrahydro-3-carboxy-pyridine) methyl and propargyl esters have been synthesized and tested for muscarinic/antimuscarinic activity on rat ileum and electrically paced left atria. Arecoline and arecaidine propargyl ester (APE) as well as their corresponding N-demethyl derivatives, Guvacoline (norarecoline) and guvacine propargyl ester, acted as full agonists at both atrial and ileal muscarinic receptors (range of pD2-values 6.09-8.07). However, in both preparations arecoline and APE were clearly more potent (up to 15-fold) than their N-demethyl analogues. Replacement of the N-methyl group in arecoline and APE by larger substituents (ethyl, n-propyl, n-butyl, benzyl, phenylethyl) as well as N-methylation resulted in a decrease or even a complete loss of agonistic activity. In both organs, the propargyl esters usually showed higher potency than the corresponding methyl ester analogues. N-Ethylguvacine propargyl ester and APE methiodide displayed pronounced agonistic activity in the atria (pD2 approximately 6.5; intrinsic activity = 0.79 and 0.67, respectively) but behaved as competitive antagonists in the ileum (pA2 = 6.06 and 5.62, respectively). Beside the lower sensitivity to muscarinic agonists of the rat ileum as compared to rat atria, the cardioselective stimulant action of both agents may also be due to their ability to recognize structural differences between atrial M2 alpha and ileal M2 beta muscarinic receptor subtypes [2].
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| ln Vivo |
Areca nuts (seeds of Areca catechu L.) are a traditional and popular masticatory in India, Bangladesh, Malaysia, certain parts of China, and some other countries. Four related pyridine alkaloids (arecoline, arecaidine, Guvacoline, and guvacine) are considered being the main functional ingredients in areca nut. Until now, A. catechu is the only known species producing these alkaloids in the Arecaceae family. In the present study, we investigated alkaloid contents in 12 Arecaceae species and found that only Areca triandra Roxb. contained these pyridine alkaloids. We further analyzed in more detail tissue-specific and development-related distribution of these alkaloids in leaves, male and female flowers and fruits in different stages of maturity in A. triandra by ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry. Results revealed that the alkaloids were most abundant in young leaves, the pericarp of ripe fruits and the endosperm of unripe fruits in developmental stage 2. Abundance of the 4 different alkaloids in A. triandra fruits varied during maturation. Pericarps of ripe fruits had the highest arecaidine concentration (4.45 mg g-1) and the lowest Guvacoline concentration (0.0175 mg g-1), whereas the endosperm of unripe fruits of developmental stage 2 contained the highest Guvacoline concentration (3.39 mg g-1) and the lowest guvacine concentration (0.245 mg g-1). We conclude that A. triandra is useful in future as a further valuable source of Areca alkaloids [1].
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| Enzyme Assay |
Alkaloid extraction from A. triandra [1]
A modified method for the extraction of alkaloids in A. triandra tissue was used (Pan et al. 2018). Samples (100 mg dry weight) were lypophilized, homogenized in a ball mill and extracted with 1.2 mL of 50% methanol containing 0.1% formic acid. The homogenate was vortexed for 2 min, sonicated for 35 min and was kept at − 20 °C for 3–5 h. The mixture was vortexed again for 3 min at room temperature, centrifuged at 10 000g for 15 min at room temperature using a refrigerated centrifuge. The supernatant was transferred to a new vial and diluted 1000 times. Samples were stored at − 20 °C until analysis. 10 μL of the samples were analyzed by UPLC-MS. Alkaloid standards were dissolved in 95% acetonitrile containing 5 mM ammonium, giving stock solutions with concentrations of 1 μg μL−1. Stock solutions were stepwise diluted with 95% acetonitrile containing 5 mM ammonium formate, giving final concentrations of 1, 2, 4, 8 and 16 pg μL−1 for arecoline and arecaidine; 40, 80, 200, 400 and 800 pg μL−1 for Guvacoline; and 100, 200, 400, 800 and 1600 pg μL−1 for guvacine, respectively. |
| Toxicity/Toxicokinetics |
201540 mouse LD50 oral 750 mg/kg European Journal of Medicinal Chemistry--Chimie Therapeutique., 26(853), 1991
201540 mouse LD50 intraperitoneal 223 mg/kg SENSE ORGANS AND SPECIAL SENSES: PTOSIS: EYE; BEHAVIORAL: SOMNOLENCE (GENERAL DEPRESSED ACTIVITY); SKIN AND APPENDAGES (SKIN): HAIR: OTHER Neuropharmacology., 21 |
| References |
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| Additional Infomation |
We were also interested in the alkaloid concentration and distribution in other plant parts. In flowers, the highest alkaloid level can be found in female flowers (1.26 mg g−1) and the lowest alkaloid concentration was detected in male flowers (0.624 mg g−1) (Fig. 4c). Guvacoline was the major alkaloid in flowers. Spadices, female flowers and male flowers contained 0.697, 0.932 and 0.360 mg g−1 Guvacoline, respectively. Arecaidine (2.74 mg g−1) was the major alkaloid in tender leaves, while Guvacoline (0.612 mg g−1) was the major alkaloid in ripe leaves (Fig. 4d). Total alkaloid contents were 5.21 times higher in tender leaves than in ripe leaves. [1]
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| Molecular Formula |
C7H12CLNO2
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|---|---|
| Molecular Weight |
177.6287
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| Exact Mass |
177.056
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| CAS # |
6197-39-3
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| Related CAS # |
Guvacoline hydrobromide; 17210-51-4
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| PubChem CID |
201540
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| Appearance |
White to off-white solid powder
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| Boiling Point |
209.1ºC at 760 mmHg
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| Melting Point |
121-122 ºC
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| Flash Point |
80.2ºC
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| LogP |
1.209
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
11
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| Complexity |
163
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| Defined Atom Stereocenter Count |
0
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| SMILES |
COC(=O)C1=CCCNC1.Cl
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| InChi Key |
ZWALOEQHJRUTKM-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C7H11NO2.ClH/c1-10-7(9)6-3-2-4-8-5-6;/h3,8H,2,4-5H2,1H3;1H
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| Chemical Name |
methyl 1,2,3,6-tetrahydropyridine-5-carboxylate;hydrochloride
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| Synonyms |
Norarecoline hydrochloride; 6197-39-3; Guvacoline hydrochloride; Guvacine methyl ester hydrochloride; DTXSID10210996; 3-Pyridinecarboxylic acid, 1,2,5,6-tetrahydro-, methyl ester, hydrochloride; 1,2,5,6-Tetrahydro-3-pyridinecarboxylic acid methyl ester hydrochloride; Nicotinic acid, 1,2,5,6-tetrahydro-, methyl ester, hydrochloride; DTXCID40133487;
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| HS Tariff Code |
2934.99.9001
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| Storage |
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 (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 36~100 mg/mL (202.7~563 mM)
Water: ~36 mg/mL Ethanol: ~36 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (14.07 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 25.0 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (14.07 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 25.0 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (14.07 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 5.6297 mL | 28.1484 mL | 56.2968 mL | |
| 5 mM | 1.1259 mL | 5.6297 mL | 11.2594 mL | |
| 10 mM | 0.5630 mL | 2.8148 mL | 5.6297 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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