5-[Br]--(4-(3,4-Dihydro-6,7-dimethoxyisoquinolin-2(1)-yl)butyl)-2,3-dimethoxybenzamide

Sigma receptors are functional, membrane-bound proteins distributed in the central nervous system (CNS) and peripheral organs such as the liver, kidneys, and endocrine glands (1, 2). The CNS sigma receptors are unique binding sites related to higher brain function. There are at least two subtypes of sigma receptors, σ and σ receptors. These receptors appear to be involved in numerous pharmacological and physiological functions, and they also modulate a number of central neurotransmitter systems. Studies have shown that these receptors may play a role in the pathogenesis of psychiatric disorders (3, 4). The σ receptors appear to play in a role in motor function and CNS disorders. The σ receptors, linked to potassium channels and calcium release, are also implicated in malignant cancers (5-7). The density of σ receptors in tumor cells was found to be greater than that of σ receptors in tumor cells. The density of σ receptors was found to be 10-fold higher in proliferating quiescent mouse mammary adenocarcinoma cells. Furthermore, σ receptor ligands were observed to induce apoptosis in tumor cells. Because of these effects, sigma receptor ligands may be useful for detection and treatment in neurology and oncology. 5-[Br]--(4-(3,4-Dihydro-6,7-dimethoxyisoquinolin-2(1)-yl)butyl)-2,3-dimethoxybenzamide ([Br]RHM-4), a conformationally flexible benzamide analog, has been shown to have a high affinity ( = 8.2 nM) and selectivity (σ/σ ratio > 1573) for σ receptors on rat liver membranes (8). [Br]RHM-4 (Br = 16.2 h) has been evaluated as a positron emission tomography (PET) agent for imaging breast tumor in mice (9).