The analgesic tropane analogue (+/-)-SM 21 has a high affinity for sigma2 receptors.
The analgesic properties of the tropane analogue (+/-)-SM 21 have been attributed to the antagonism of presynaptic m2 receptors resulting in a potentiation of acetylcholine release. However, drugs targeting a number of other neurotransmitter receptors have been shown to enhance acetylcholine release. In the current study, in vitro studies were conducted in order to determine the affinity of (+/-)-SM 21 for serotonin 5-HT3, 5-HT4, and sigma receptors. Our results indicate that (+/-)-SM 21, and its structural congeners, have a relatively high affinity for sigma2 receptors relative to their reported affinity for muscarinic receptors. The higher affinity for sigma2 versus sigma1 receptors indicates that (+/-)-SM 21 may be a suitable lead compound for developing sigma2-selective ligands.
Mach
R H
RH
Department of Radiology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Wu
L
L
West
T
T
Whirrett
B R
BR
Childers
S R
SR
D000700:Analgesics / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001285:Atropine / Q000737:chemistry / Q000378:metabolism; D001562:Benzimidazoles / Q000737:chemistry / Q000378:metabolism; D001590:Benztropine / Q000737:chemistry / Q000378:metabolism; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry / Q000378:metabolism; D002087:Butyrates / Q000737:chemistry / Q000378:metabolism*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008024:Ligands; D018727:Muscarinic Antagonists / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D011985:Receptors, Serotonin / Q000378:metabolism; D044406:Receptors, Serotonin, 5-HT3; D044422:Receptors, Serotonin, 5-HT4; D017480:Receptors, sigma / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D014326:Tropanes / Q000737:chemistry / Q000378:metabolism*; D000097605:Sigma-1 Receptor
D000700:Analgesics; D001285:Atropine; D001562:Benzimidazoles; D001590:Benztropine; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002087:Butyrates; D008024:Ligands; D018727:Muscarinic Antagonists; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D044422:Receptors, Serotonin, 5-HT4; D017480:Receptors, sigma; D012702:Serotonin Antagonists; D014326:Tropanes; D000097605:Sigma-1 Receptor; C106107:sigma-2 receptor; C070187:(endo-N-8-methyl-8-azabicyclo(3.2.1)oct-3-yl)-2,3-dihydro-3-ethyl-2-oxo-1H-benzimidazol-1-carboxamide; C107044:SM 21; C042253:bemesetron