BIMU 8

5-HT4 agonist CAS# 134296-40-5

BIMU 8

Catalog No. BCC7928----Order now to get a substantial discount!

Product Name & Size Price Stock
BIMU 8: 5mg $104 In Stock
BIMU 8: 10mg Please Inquire In Stock
BIMU 8: 20mg Please Inquire Please Inquire
BIMU 8: 50mg Please Inquire Please Inquire
BIMU 8: 100mg Please Inquire Please Inquire
BIMU 8: 200mg Please Inquire Please Inquire
BIMU 8: 500mg Please Inquire Please Inquire
BIMU 8: 1000mg Please Inquire Please Inquire
Related Products

Quality Control of BIMU 8

Number of papers citing our products

Chemical structure

BIMU 8

3D structure

Chemical Properties of BIMU 8

Cas No. 134296-40-5 SDF Download SDF
PubChem ID 131724 Appearance Powder
Formula C19H27ClN4O2 M.Wt 378.9
Type of Compound N/A Storage Desiccate at -20°C
Solubility Soluble to 75 mM in water and to 100 mM in DMSO
Chemical Name N-(8-methyl-8-azabicyclo[3.2.1]octan-3-yl)-2-oxo-3-propan-2-ylbenzimidazole-1-carboxamide;hydrochloride
SMILES CC(C)N1C2=CC=CC=C2N(C1=O)C(=O)NC3CC4CCC(C3)N4C.Cl
Standard InChIKey NQYXXIUVFVOJCX-UHFFFAOYSA-N
Standard InChI InChI=1S/C19H26N4O2.ClH/c1-12(2)22-16-6-4-5-7-17(16)23(19(22)25)18(24)20-13-10-14-8-9-15(11-13)21(14)3;/h4-7,12-15H,8-11H2,1-3H3,(H,20,24);1H
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months.
Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it.
About Packaging 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial.
2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial.
3. Try to avoid loss or contamination during the experiment.
Shipping Condition Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request.

Biological Activity of BIMU 8

DescriptionPotent 5-HT4 receptor full agonist (KD = 77 nM and EC50 = 18 nM for wild type 5-HT4 receptors). Binds to receptors in a mechanism different to that of the endogenous ligand 5-HT.

BIMU 8 Dilution Calculator

Concentration (start)
x
Volume (start)
=
Concentration (final)
x
Volume (final)
 
 
 
C1
V1
C2
V2

calculate

BIMU 8 Molarity Calculator

Mass
=
Concentration
x
Volume
x
MW*
 
 
 
g/mol

calculate

Preparing Stock Solutions of BIMU 8

1 mg 5 mg 10 mg 20 mg 25 mg
1 mM 2.6392 mL 13.1961 mL 26.3922 mL 52.7844 mL 65.9805 mL
5 mM 0.5278 mL 2.6392 mL 5.2784 mL 10.5569 mL 13.1961 mL
10 mM 0.2639 mL 1.3196 mL 2.6392 mL 5.2784 mL 6.598 mL
50 mM 0.0528 mL 0.2639 mL 0.5278 mL 1.0557 mL 1.3196 mL
100 mM 0.0264 mL 0.132 mL 0.2639 mL 0.5278 mL 0.6598 mL
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations.

Organizitions Citing Our Products recently

 
 
 

Calcutta University

University of Minnesota

University of Maryland School of Medicine

University of Illinois at Chicago

The Ohio State University

University of Zurich

Harvard University

Colorado State University

Auburn University

Yale University

Worcester Polytechnic Institute

Washington State University

Stanford University

University of Leipzig

Universidade da Beira Interior

The Institute of Cancer Research

Heidelberg University

University of Amsterdam

University of Auckland
TsingHua University
TsingHua University
The University of Michigan
The University of Michigan
Miami University
Miami University
DRURY University
DRURY University
Jilin University
Jilin University
Fudan University
Fudan University
Wuhan University
Wuhan University
Sun Yat-sen University
Sun Yat-sen University
Universite de Paris
Universite de Paris
Deemed University
Deemed University
Auckland University
Auckland University
The University of Tokyo
The University of Tokyo
Korea University
Korea University

Background on BIMU 8

BIMU 8 is an agonist of 5-HT4 with Ki values of 33.9 ± 8.0 nM and 12.6 ± 0.9 nM in guinea pig ileum and striatum, respectively [1, 2].

As a member of the seven transmembrane spanning G-protein-coupled family of receptors, the 5-HT4 receptor is positively coupled to adenylate cyclase. It exists in two isoforms (5-HT4S and 5-HT4L). These two isoforms differ in the sequence and length of their carboxy termini [3].

BIMU 8 significantly decreased the K+ current in colliculi neurons. This suggested a 5-HT4 receptor-mediated effect [4]. In neurons, BIMU 8 at concentrations ranging from 0.003-0.1 µM increased EPSP amplitude but did not change membrane potential. The EPSP potentiation induced by BIMU 8 was blocked by tropisetron (1 µM), a 5-HT3/5-HT4 receptor antagonist. But ondansetron (1 µM), a 5-HT3 receptor antagonist did not blocked the EPSP potentiation induced by BIMU 8 [5].

In the hot-plate test, BIMU 8 injected i.p. in the range of doses of 20-30 mg/kg significantly induced an increase in the pain threshold. 15 min after administration, the antinociceptive effect reached a maximum and hence diminished. This effect disappeared within 45 min. Choline uptake blocker HC-3 (1 µg per mouse i.c.v.), antimuscarinic drug atropine (5 mg/kg i.p.), 5-HT4 antagonists SDZ 205-557 (10 mg/kg i.p.) and GR 125487 (20 mg/kg i.p.) completely prevented the antinociception of BIMU 8 [1].

References:
[1].  Ghelardini C, Galeotti N, Casamenti F, et al. Central cholinergic antinociception induced by 5HT4 agonists: BIMU 1 and BIMU 8. Life sciences, 1996, 58(25): 2297-2309.
[2].  Yoshikawa T, Yoshida N, Mine Y, et al. Affinity of mosapride citrate, a new gastroprokinetic agent, for 5-HT4 receptors in guinea pig ileum. The Japanese Journal of Pharmacology, 1998, 77(1): 53-59.
[3].  Hegde SS, Eglen RM. Peripheral 5-HT4 receptors. The FASEB journal, 1996, 10(12): 1398-1407.
[4].  Fagni L, Dumuis A, Sebben M, et al. The 5-HT4 receptor subtype inhibits K+ current in colliculi neurones via activation of a cyclic AMP-dependent protein kinase. British journal of pharmacology, 1992, 105(4): 973-979.
[5].  Pan H, Galligan JJ. 5-HT1A and 5-HT4 receptors mediate inhibition and facilitation of fast synaptic transmission in enteric neurons. American Journal of Physiology-Gastrointestinal and Liver Physiology, 1994, 266(2): G230-G238.

Featured Products
New Products
 

References on BIMU 8

Central cholinergic antinociception induced by 5HT4 agonists: BIMU 1 and BIMU 8.[Pubmed:8649219]

Life Sci. 1996;58(25):2297-309.

The antinociceptive effect of two 5-HT4 agonists, BIMU 1 and BIMU 8, were examined in mice and rats by using the hot-plate, abdominal constriction and paw-pressure tests. In both species, BIMU 1 (10-20 mg kg-1 s.c. and 40-60 mg kg-1 p.o. in mice; 20 mg kg-1 i.p. in rats) and BIMU 8 (20-30 mg kg-1 s.c. and 60 mg kg-1 p.o. in mice; 20 mg kg-1 i.p. in rats), produced significant antinociception which was prevented by atropine (5 mg kg-1 i.p.), hemicholinium-3 (1 microgram per mouse i.c.v.), SDZ 205-557 (10 mg kg-1 i.p.), GR 125487 (20 mg kg-1 i.p.) but not by naloxone (1 mg kg-1 i.p.), CGP 35348 (100 mg kg-1 i.p.) and reserpine (2 mg kg-1 i.p.). Moreover, BIMU 1 and BIMU 8 increase of pain threshold, is abolished by nucleus basalis magnocellularis (NBM) lesions in rats. SDZ 205-557 and GR 125487 which totally antagonized BIMU 1 and BIMU 8 antinociception did not modify morphine (7 mg kg-1 s.c.) or baclofen (4 mg kg-1 s.c.) antinociception. Intracerebroventricular injection in mice of BIMU 1 (3 micrograms per mouse) and BIMU 8 (10 micrograms per mouse), doses which were largely ineffective by parenteral routes, induces an antinociception whose intensity equaled that obtainable s.c., i.p. or p.o. In the antinociceptive dose-range, neither 5HT4 agonist impaired mice motor coordination evaluated by rota-rod test. On the basis of the above data, it can be postulated that BIMU 1 and BIMU 8 exerted an antinociceptive effect mediated by a central amplification of cholinergic transmission.

Conformational toggle switches implicated in basal constitutive and agonist-induced activated states of 5-hydroxytryptamine-4 receptors.[Pubmed:19168624]

Mol Pharmacol. 2009 Apr;75(4):982-90.

The extended classic ternary complex model predicts that a G protein-coupled receptor (GPCR) exists in only two interconvertible states: an inactive R, and an active R(*). However, different structural active R(*) complexes may exist in addition to a silent inactive R ground state (Rg). Here we demonstrate, in a cellular context, that several R(*) states of 5-hydroxytryptamine-4 (5-HT(4)) receptors involve different side-chain conformational toggle switches. Using site-directed mutagenesis and molecular modeling approaches, we show that the basal constitutive receptor (R(*)basal) results from stabilization of an obligatory double toggle switch (Thr3.36 from inactive g- to active g+ and Trp6.48 from inactive g+ to active t). Mutation of either threonine or tryptophan to alanine resulted in a lowering of the activity of the R(*)basal similar to the Rg. The T3.36A mutation shows that the Thr3.36 toggle switch plays a minor role in the stabilization of R(*) induced by 5-HT (R(*)-5-HT) and BIMU8 (R(*)-BIMU8) and is fully required in the stabilization of R(*) induced by (S)-zacopride, cisapride, and 1-(4-amino-5-chloro-2-methoxyphenyl)-3-(1-butyl-4-piperidinyl)-1-propanone (RS 67333) (R(*)-benzamides). Thus, benzamides stabilize R(*)-benzamides by forming a specific hydrogen bond with Thr3.36 in the active g+ conformation. Conversely, R(*)-BIMU8 was probably the result of a direct conformational transition of Trp6.48 from inactive g+ to active t by hydrogen bonding of this residue to a carboxyl group of BIMU8. We were surprised that the Trp6.48 toggle switch was not necessary for receptor activation by the natural agonist 5-HT. R(*)-5-HT is probably attained through other routes of activation. Thus, different conformational arrangements occur during stabilization of R(*)basal, R(*)-5-HT, R(*)-benzamides, and R(*)-BIMU8.

Synthesis and structure-activity relationships of potent and orally active 5-HT4 receptor antagonists: indazole and benzimidazolone derivatives.[Pubmed:9599243]

J Med Chem. 1998 May 21;41(11):1943-55.

A series of indole-3-carboxamides, indazole-3-carboxamides, and benzimidazolone-3-carboxamides was synthesized and evaluated for antagonist affinity at the 5-HT4 receptor in the rat esophagus. The endo-3-tropanamine derivatives in the indazole and benzimidazolone series possessed greater 5-HT4 receptor affinity than the corresponding indole analogues. 5-HT4 receptor antagonist affinity was further increased by alkylation at N-1 of the aromatic heterocycle. In a series of 1-isopropylindazole-3-carboxamides, replacement of the bicyclic tropane ring system with the monocyclic piperidine ring system or an acyclic aminoalkylene chain led to potent 5-HT4 receptor antagonists. In particular, those systems in which the basic amine was substituted with groups capable of forming hydrogen bonds showed increased 5-HT4 receptor antagonist activity. While some of these compounds displayed high affinity for other neurotransmitter receptors (in particular, 5-HT3, alpha1, and 5-HT2A receptors), as the conformational flexibility of the amine moiety increased, the selectivity for the 5-HT4 receptor also increased. From this series of compounds, we identified LY353433 (1-(1-methylethyl)-N-[2-[4-[(tricyclo[3.3.1.1(3, 7)]dec-1-ylcarbonyl)amino]-1-piperidinyl]ethyl]-1H-indazole-3- carboxamide) as a potent and selective 5-HT4 receptor antagonist with clinically suitable pharmacodynamics.

Description

Potent 5-HT4 receptor full agonist

Keywords:

BIMU 8,134296-40-5,Natural Products,5-HT Receptor, buy BIMU 8 , BIMU 8 supplier , purchase BIMU 8 , BIMU 8 cost , BIMU 8 manufacturer , order BIMU 8 , high purity BIMU 8

Online Inquiry for:

      Fill out the information below

      • Size:Qty: - +

      * Required Fields

                                      Result: