Pharmacological identification of SM-21, the novel sigma(2) antagonist.
SM-21 is a tropane analogue with high affinity and selectivity for sigma(2) receptor subtype. In the absence of highly selective sigma(2) antagonists, the aim of the present study was to determine whether SM-21 is endowed with antagonistic activity. The experiments were conducted in rats by inducing neck dystonia, which is reported to be subsequent to activation of sigma(2) receptors. SM-21 (10 nmol/0.5 microl) was able to prevent torsion of the neck obtained by administration of the sigma(1)-sigma(2) agonist 1,3-di-(2-tolyl)guanidine (DTG, 5 nmol/0.5 microl) in the red nucleus. These data indicate that SM-21 is a potent and selective sigma(2) antagonist.
Ghelardini
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C
Department of Preclinical and Clinical Pharmacology, Viale G. Pieraccini 6, University of Florence, I-50139, Florence, Italy. ghelard@server1.pharm.unifi.it
Galeotti
N
N
Bartolini
A
A
D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects; D002087:Butyrates / Q000627:therapeutic use*; D006146:Guanidines / Q000009:adverse effects; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017480:Receptors, sigma / Q000037:antagonists & inhibitors* / Q000502:physiology; D012012:Red Nucleus / Q000187:drug effects* / Q000502:physiology; D014103:Torticollis / Q000139:chemically induced / Q000188:drug therapy*; D014326:Tropanes / Q000627:therapeutic use*
D000700:Analgesics; D000927:Anticonvulsants; D002087:Butyrates; D006146:Guanidines; D017480:Receptors, sigma; D014326:Tropanes; C106107:sigma-2 receptor; C107044:SM 21; C050232:1,3-ditolylguanidine