Binding of β‐Carbolines and Tetrahydroisoquinolines by Opiate Receptors of the δ‐Type

Abstract

Effects of various β‐carbolines (BC's) and two tetrahydroisoquinolines (TIQ's) on the specific binding of a natural opiate δ‐receptor ligand, leucine enkephalin, have been studied in rat synaptosomal membranes, and compared with the effects on the binding of mu‐receptor ligands dihydromorphine and naloxone. Harmaline (7‐MeO‐1‐Me‐dihydro‐BC) was the most potent compound studied (Ki value 3.5 μM), while the two TIQ's (salsolinol and salsolidine) were less potent than BC's (Ki> 100 μM) in inhibiting the binding of δ‐receptors. In general, BC's showed more affinity for δ‐receptors than for μ‐receptors; salsolinol was more potent against the binding of μ‐receptors. Inhibition of binding was generally of the competitive type: Kd values increased and Bmax values were not altered. The Na dependence suggests that BC's and salsolinol are antagonists or partial agonists of opioids. Since the binding affinity of BC's and TIQ's was on the micromolar level only, the opiate receptors do not appear to be the major sites of action for BC's or TIQ's.

What is in that Drink: The Biological Actions of Ethanol, Acetaldehyde, and Salsolinol

“…SAL has been shown to significantly decrease striatal levels of 5-HT metabolic enzymes, subsequently increasing 5-HT to a levels 20 fold higher than DA (Nakahara et al, 1994). Additionally, SAL has been shown to possess a high affinity for the μ (MOR) opioid receptor (Airaksinen et al, 1984). SAL-induced locomotor activity, conditioned place preference, and stimulated DA release in the AcbSh can be reduced by microinjections of MOR antagonists into the posterior VTA (Hipolito et al, 2010, 2011).…”

What is in that Drink: The Biological Actions of Ethanol, Acetaldehyde, and Salsolinol

“…SAL has been shown to significantly decrease striatal levels of 5-HT metabolic enzymes, subsequently increasing 5-HT to a levels 20 fold higher than DA (Nakahara et al, 1994). Additionally, SAL has been shown to possess a high affinity for the μ (MOR) opioid receptor (Airaksinen et al, 1984). SAL-induced locomotor activity, conditioned place preference, and stimulated DA release in the AcbSh can be reduced by microinjections of MOR antagonists into the posterior VTA (Hipolito et al, 2010(Hipolito et al, , 2011.…”

“…Infusion of TBC into the hippocampus of low alcohol drinking (LAD) rats increased alcohol preference and consumption (Adell & Myers, 1995;Huttunen & Myers, 1987) through increases in both 5-HT and norepinephrine levels (Adell & Myers, 1995). TBCs exhibit an affinity for the δ opioid receptor (DOR) (Airaksinen et al, 1984), but the pharmacological properties of TBCs have not been fully examined.…”

Enhanced dopamine D2 receptor function in hypothalamus and corpus striatum: their role in liver, plasma and in vitro hepatocyte ALDH regulation in ethahol treated rats

“…Enhanced 5-HT 2A receptor status in the hypothalamus and corpus striatum of ethanol treated rats was reported [43]. Ethanol also acts directly through the production of neuroamines that interact with dopaminergic systems [13,44]. DA receptor antagonists attenuate the locomotor-activating effects of acute ethanol, suggesting an important role of mesolimbic DA neurons in mediating the acute effects of ethanol [45][46][47].…”