Many antidepressant drugs interact with σ receptors and accumulating evidence suggests that these proteins mediate antidepressant-like effects in animals and humans. σ Receptors are localized in brain regions affected in depression, further strengthening the hypothesis that they represent logical drug development targets. In this study, two novel σ receptor agonists (UMB23, UMB82) were evaluated for antidepressant-like activity in mice. First, radioligand binding studies confirmed that the novel compounds had preferential affinity for σ receptors. Second, the forced swim test, a well established animal model for screening potential antidepressant drugs, showed that both compounds dose-dependently reduced immobility time. The σ receptor antagonist BD1047 attenuated the antidepressant-like effects of UMB23 and UMB82. Third, locomotor activity suggested that the effects of UMB23 and UMB82 in the forced swim test were not due to non-specific motor activating effects. Together, the data provide further evidence that σ receptor agonists represent a possible new class of antidepressant medication.

Earlier studies have demonstrated that antagonism of σ 1 receptors attenuates the convulsive, lethal, locomotor stimulatory and rewarding actions of cocaine in mice. In contrast, the contribution of σ 2 receptors is unclear because experimental tools to selectively target this subtype are unavailable. To begin addressing this need, we characterized UMB24 (1-(2-phenethyl)-4-(2-pyridyl)-piperazine) and (±)-SM 21 (3α-tropanyl-2-(4-chorophenoxy)butyrate) in receptor binding and behavioral studies. Receptor binding studies confirmed that UMB24 and (±)-SM 21 display preferential affinity for σ 2 over σ 1 receptors. In behavioral studies, pretreatment of Swiss Webster mice with UMB24 or (±)-SM 21 significantly attenuated cocaine-induced convulsions and locomotor activity, but not lethality. When administered alone, (±)-SM 21 produced no significant effects compared to control injections of saline, but UMB24 had locomotor depressant actions. Together, the data suggest that σ 2 receptor antagonists have the potential to attenuate some of the behavioral effects of cocaine, and further development of more selective, high affinity ligands are warranted.

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Introduction —An arteriovenous fistula between the subclavian artery and the internal jugular vein represents a rare iatrogenic injury that has almost exclusively been described on the right side. We describe the case of an arteriovenous fistula between the left subclavian artery and the left internal jugular vein after attempted central venous cannulation. The initial duplex ultrasound exam established the definitive diagnosis. Patient Description —A 72-year-old man had a central venous catheter inadvertently placed in the arterial system during attempted cannulation of the left internal jugular vein. After the catheter was removed, a duplex ultrasound exam of the left common carotid artery was requested to evaluate for injury. Methods —A carotid duplex ultrasound exam was performed using an Acuson Antares Ultrasound System with a VFX 9–4 MHz probe. The left common, internal, and external carotid arteries were evaluated with grayscale imaging; color Doppler, and spectral flow analysis. The left vertebral artery and subclavian arteries were also evaluated sonographically. Results —The duplex ultrasound did not detect an injury to the left common carotid artery; however, a color flow bruit was noted in the surrounding tissue. Further investigation clearly demonstrated a high-flow vascular communication between the left subclavian artery and the left internal jugular vein consistent with an arteriovenous fistula. The arteriovenous fistula was treated with an endovascular intervention that involved placing a stent graft in the left subclavian artery to cover the arterial origin of the arteriovenous fistula. The completion arteriogram and follow-up duplex ultrasound showed that the stent graft completely excluded the arteriovenous fistula. Conclusion —This case describes an extremely rare iatrogenic arteriovenous fistula between the left subclavian artery and the left internal jugular vein. The images obtained with duplex sonography were detailed enough to definitively diagnose the injury and plan for treatment.