AChR/nicotinic acetylcholine receptors

Adherens junctions break down when Caco-2 cells are treated with the AChR antagonist vasocurarine (10 µM). The effect of the vasocurarine AChR antagonist on Caco-2 cell adherens junctions is lessened by buffalo milk cow's milk (MBCP) (18 µM) [1].

It has been reported that several aminoglycoside antibiotics have a potential of prolonging the action of non-depolarizing muscle relaxants by drug interactions acting pre-synaptically to inhibit acetylcholine release, but antibiotics itself also have a strong effect on relaxing the smooth muscle. In this study, four antibiotics of aminoglycosides such as gentamicin, streptomycin, kanamycin and neomycin were compared with skeletal muscle relaxants baclofen, Tubocurarine Chloride, pancuronium and succinylcholine, and a smooth muscle relaxant, papaverine. The muscle strips isolated from the rat bladder were stimulated with pulse trains of 40 V in amplitude and 10 s in duration, with pulse duration of 1 ms at the frequency of 1-8 Hz, at 1, 2, 4, 6, 8 Hz respectively. To test the effect of four antibiotics on bladder smooth muscle relaxation, each of them was treated cumulatively from 1 μM to 0.1 mM with an interval of 5 min. Among the four antibiotics, gentamicin and neomycin inhibited the EFS response. The skeletal muscle relaxants (baclofen, Tubocurarine Chloride, pancuronium and succinylcholine) and inhibitory neurotransmitters (GABA and glycine) did not show any significant effect. However, papaverine, had a significant effect in the relaxation of the smooth muscle. It was suggested that the aminoglycoside antibiotics have inhibitory effect on the bladder smooth muscle.[2]

Assessment of drug responses [2]
Concentration–response curve to antibiotics such as gentamicin (1 μM–0.1 mM), streptomycin (1 μM–0.1 mM), kanamycin (1 μM–0.1 mM), neomycin (1 μM–0.1 mM); muscle relaxants such as baclofen (0.1 mM), Tubocurarine Chloride (0.1 mM), pancuronium (0.1 mM), succinylcholine (0.1 mM), and papaverine (0.1 mM); and neurotransmitters GABA (0.1 mM) and glycine (0.1 mM); were established by increasing the concentration of the drug added to the organ bath with a 30 min contact time. For each dose, EFS of 1–8 Hz was given. Muscle strips were washed with Kreb’s solution for five times and equilibrated for 30 min between each part within the sets of experiments. All drugs were added to the organ bath in volumes not exceeding 100 µl (10 % organ bath volume).

man TDLo intravenous 150 ug/kg SENSE ORGANS AND SPECIAL SENSES: PTOSIS: EYE; VASCULAR: BP LOWERING NOT CHARACTERIZED IN AUTONOMIC SECTION; LUNGS, THORAX, OR RESPIRATION: DYSPNEA Journal of Pharmacology and Experimental Therapeutics., 93(109), 1948
rat LD50 intraperitoneal 270 ug/kg VASCULAR: BP LOWERING NOT CHARACTERIZED IN AUTONOMIC SECTION Journal of Pharmacology and Experimental Therapeutics., 97(19), 1949
mouse LD50 oral 150 mg/kg LUNGS, THORAX, OR RESPIRATION: DYSPNEA Journal of Pharmacology and Experimental Therapeutics., 118(395), 1956 [PMID:13385800]

[1]. Intestinal Anti-Inflammatory Effect of a Peptide Derived from Gastrointestinal Digestion of Buffalo (Bubalus bubalis) Mozzarella Cheese. Nutrients. 2019 Mar 13;11(3). pii: E610.

[2]. The comparative effects of aminoglycoside antibiotics and muscle relaxants on electrical field stimulation response in rat bladder smooth muscle. Arch Pharm Res. 2016 Jun;39(6):863-70.

[3]. The crystal and molecular structure of a potent neuromuscular blocking agent: d-tubocurarine dichloride pentahydrate. Acta Cryst. (1973). B29, 935.

Tubocurarine Chloride is the chloride salt form of tubocurarine, a naturally occurring curare alkaloid isolated from the bark and stem of Chondodendron tomentosum with a muscle relaxant property. Tubocurarine chloride competes with acetylcholine for the nicotinic receptors at the neuromuscular junction of skeletal muscles, thereby inhibiting the action of acetylcholine and blocking the neural transmission without depolarizing the postsynaptic membrane. This may lead to skeletal muscle relaxation and paralysis.
A neuromuscular blocker and active ingredient in CURARE; plant based alkaloid of Menispermaceae.
See also: Tubocurarine Chloride (annotation moved to).

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Under physiological conditions, the small intestine represents a barrier against harmful antigens and pathogens. Maintaining of the intestinal barrier depends largely on cell⁻cell interactions (adherent-junctions) and cell⁻matrix interactions (tight-junctions). Inflammatory bowel disease is characterized by chronic inflammation, which induces a destructuring of the architecture junctional epithelial proteins with consequent rupture of the intestinal barrier. Recently, a peptide identified by Bubalus bubalis milk-derived products (MBCP) has been able to reduce oxidative stress in intestinal epithelial cells and erythrocytes. Our aim was to evaluate the therapeutic potential of MBCP in inflammatory bowel disease (IBD). We studied the effect of MBCP on (i) inflamed human intestinal Caco2 cells and (ii) dinitrobenzene sulfonic acid (DNBS) mice model of colitis. We have shown that MBCP, at non-cytotoxic concentrations, both in vitro and in vivo induced the adherent epithelial junctions organization, modulated the nuclear factor (NF)-κB pathway and reduced the intestinal permeability. Furthermore, the MBCP reverted the atropine and tubocurarine injury effects on adherent-junctions. The data obtained showed that MBCP possesses anti-inflammatory effects both in vitro and in vivo. These results could have an important impact on the therapeutic potential of MBCP in helping to restore the intestinal epithelium integrity damaged by inflammation.[1]

C37H52CL2N2O11

771.7216

770.295

C, 57.59; H, 6.79; Cl, 9.19; N, 3.63; O, 22.80

6989-98-6

57-94-3 (chloride); 57-94-4; 6989-98-6 (chloride pentahydrate)

23422

White to off-white solid powder

1.2074 (rough estimate)

275-280ºC (dec.)(lit.)

193 ° (C=1, H2O)

4.082

8

13

2

52

990

2

CN1CCC2=CC(=C3C=C2[C@@H]1CC4=CC=C(C=C4)OC5=C6[C@@H](CC7=CC(=C(C=C7)O)O3)[N+](CCC6=CC(=C5O)OC)(C)C)OC.O.O.O.O.O.Cl.[Cl-]

WMIZITXEJNQAQK-GGDSLZADSA-N

InChI=1S/C37H40N2O6.2ClH.5H2O/c1-38-14-12-24-19-32(42-4)33-21-27(24)28(38)16-22-6-9-26(10-7-22)44-37-35-25(20-34(43-5)36(37)41)13-15-39(2,3)29(35)17-23-8-11-30(40)31(18-23)45-33;;;;;;;/h6-11,18-21,28-29H,12-17H2,1-5H3,(H-,40,41);2*1H;5*1H2/t28-,29+;;;;;;;/m0......./s1

(1S,16R)-10,25-dimethoxy-15,15,30-trimethyl-7,23-dioxa-30-aza-15-azoniaheptacyclo[22.6.2.23,6.18,12.118,22.027,31.016,34]hexatriaconta-3(36),4,6(35),8(34),9,11,18(33),19,21,24,26,31-dodecaene-9,21-diol;chloride;pentahydrate;hydrochloride

6989-98-6; (+)-Tubocurarine chloride pentahydrate; Tubocurarine chloride; d-Tubocurarine chloride pentahydrate; (+)-Tubocurarine chloride hydrochloride pentahydrate; Tubaine; TUBOCURARINE CHLORIDE PENTAHYDRATE; D-Tubocurarine (chloride pentahydrate);

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)

MEthanol : ~83.33 mg/mL (~107.98 mM)
DMSO : ~33.33 mg/mL (~43.19 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (3.24 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.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (3.24 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.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (3.24 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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