Acetylcholine
The class of transmembrane acetylcholine receptors can be divided into two main groups: the muscarinic (metabotropic) and the nicotinergic (ionotropic) receptors. This as a result of the specific binding affinities once determined of the two types of receptors for muscarine and nicotine respectively[1],[2]. The latter type is classified as a ligand gated ion channel, since activation of this receptor allows sodium ions to enter a cells interior and potassium and/or calcium ions to exit (section Ion channels (Ligand gated, Cys-loop, cationic)[3]. Unlike the nicotinergic acetylcholine receptor, the muscarinic type is part of the family of G-protein coupled receptors (GPCR-A18). In general, muscarinic acetylcholine receptors are known to play highly important and diverse roles in many basic physiological processes including gastrointestinal, cardiovascular, motor, attention, learning, memory, pain, sleep, and other functions[4]. Four subtypes have been identified, localized and characterized (M1-M4), whereas a fifth member has been cloned (M5), yet its function has not been revealed completely[5],[6]. In order to facilitate the study of this most recent addition to the family of mACh receptors, Axon Medchem offers VU 0238429 (Axon 1786) as a high affinity drug (EC50 of approximately 1.16 µM at M5) with >30-fold selectivity versus M1 and M3, and no M2 or M4 potentiator activity.
[1] The pharmacology of flaxedil with observations on certain analogs. Riker WF, Wescoe WC. Ann NY Acad Sci 1951, 54, 373–394.
[2] The Chemical Transmission of Nerve Action. O. Loewi. Nobel Lecture,December 12, 1936.
[3] Purves, Dale, George J. Augustine, David Fitzpatrick, William C. Hall, Anthony-Samuel LaMantia, James O. McNamara, and Leonard E. White (2008). Neuroscience. 4th ed.. Sinauer Associates. pp. 122–6. ISBN 978-0-87893-697-7.
[4] Cloning and Expression of the Human and Rat m5 Muscarinic Acetylcholine Receptor Genes. Bonner, T. I.; Young, A. C.; Brann, M. R.; Buckley, N. J. Neuron 1988, 1, 403–410.
[5] Muscarinic acetylcholine receptor subtypes: localization and structure/function. Brann MR, Ellis J, Jørgensen H, Hill-Eubanks D, Jones SV. Prog Brain Res. 1993, 98, 121-7.
[6] Discovery of the first highly M5-preferring muscarinic acetylcholine receptor ligand, an M5 positive allosteric modulator derived from a series of 5-trifluoromethoxy N-benzyl isatins. Bridges TM, Marlo JE, Niswender CM, et al. J. Med. Chem. 2009, 52, 3445–8.
Axon ID | Name | Description | From price | |
---|---|---|---|---|
3669 | (S)-(+)-Dimethindene maleate | Potent and selective M2 muscarinic receptor antagonist | €125.00 | |
3513 | Bethanechol chloride | Muscarinic receptor (mAChR) agonist | €50.00 | |
1146 | Clozapine | Atypical antipsychotic | €50.00 | |
2796 | Clozapine N-oxide | Muscarinic DREADD agonist | €95.00 | |
3965 | Deschloroclozapine | Potent, selective, brain penetrable DREADD agonist | €90.00 | |
4086 | Emraclidine | Highly selective, brain-penetrant PAM of M4 mAChR | €140.00 | |
1289 | GMC 1-109 | Clozapine analog devoid of DA, 5-HT2, H1 and α1 affinities, but with high M1 affinity | €125.00 | |
2851 | GMC 1-161 | Clozapine analog with 5-HT2A, M1 and D2 affinity, devoid of D1 affinities | €135.00 | |
1152 | GMC 1-165 | Clozapine analog with 5-HT2A and M1 affinity, devoid of D1/D2 affinities | €135.00 | |
3280 | JHU37152 | Potent and CNS-active DREADD agonist | €90.00 | |
3281 | JHU37160 | Potent and CNS-active DREADD agonist | €90.00 | |
1679 | MDL 201012 | Muscarinic M3 antagonist | €110.00 | |
1298 | Olanzapine | Atypical antipsychotic | €75.00 | |
3505 | Oxybutynin hydrochloride | Competitive M1/M2/M3 mAChR antagonist | €50.00 | |
3286 | Penehyclidine hydrochloride | Anticholinergic drug | €130.00 | |
2463 | TBPB | Allosteric activator of the M1 acetylcholine receptor devoid of M2-M5 activity. | €105.00 | |
2049 | Tolterodine L-tartrate | Muscarinic receptor (mAChR) antagonist | €60.00 | |
3648 | Trospium chloride | Specific, orally active and competitive muscarinic receptor (mAChR) antagonist | €60.00 | |
1988 | VU 0029767 | PAM of mAChR M1 that potentiates the agonistic effect of Ach | €110.00 | |
1483 | VU 0152100 | PAM of M4 mAChR | €85.00 | |
1786 | VU 0238429 | Selective PAM of M5 mAChR (CHRM5) | €105.00 | |
1787 | VU 0255035 | Selective M1 mAChR Antagonist | €120.00 | |
1703 | VU 0357017 hydrochloride | PAM of M1 mAChR | €115.00 | |
1943 | VU 0365114 | Selective PAM of M5 mAChR (CHRM5) | €115.00 | |
2739 | VU 6008667 | Selective NAM of M5 mAChR (CHRM5) | €105.00 | |
3271 | VU0486846 | Potent and highly selective PAM of M1 mAChR | €165.00 | |
1273 | Zamifenacin fumarate | Muscarinic M3 antagonist | €130.00 |