Interaction of catecholamine‐derived alkaloids with central neurotransmitter receptors

Abstract

Catecholamine-derived alkaloids of the simple tetrahydroisoquinoline, 1-benzyl-tetrahydroisoquinoline and tetrahydroprotoberberine classes have been tested for their ability to inhibit the binding of seven different radioligands to neurotransmitter receptors of brain synaptic membranes. Alkaloids of all three classes were active in inhibiting 3H-clonidine binding to alpha 2-adrenergic receptors. Stereoselectivity of tetrahydropapaveroline in binding to alpha 2-adrenergic receptors was evidenced by the marked activity of the S-(--) isomer (IC50 = 0.65 microM) in comparison to the R-(+) enantiomer (IC50 = 50 microM). The simple tetrahydroisoquinolines (3,4-dihydroxytetrahydroisoquinoline and salsolinol), the four isomeric mono-O-methyl derivatives of 2,3,10,11-tetrahydroxyberbine and tetrahydropapaveroline were the most potent inhibitors of 3H-apomorphine binding to dopaminergic receptor agonist sites. The tetrahydroprotoberberines, as a class, were the most potent inhibitors of 3H-spiroperidol binding to dopaminergic receptor antagonist sites and of 3H-WB-4101 binding to alpha 1-adrenergic receptors. The 1-benzyl-tetrahydroisoquinolines exhibited varying degrees of interaction with beta 1-adrenergic receptors. Tetrahydropapaveroline (IC50 = 0.3 microM) was the most active of the 24 alkaloids tested in inhibiting binding of 3H-dihydroalprenolol to beta 1-adrenergic receptors. None of the alkaloids significantly affected 3H-QNB binding to muscarinic-cholinergic receptors, and selected alkaloids from each class interacted only moderately with serotonergic receptors.

Cholinergic Regulation of Morphine Release from Human White Blood Cells: Evidence for a Novel Nicotinic Receptor via Pharmacological and Micro Array Analysis

“…Interestingly, nicotine stimulates dopamine release and induces tyrosine hydroxylase mRNA expression in rat adrenal tissues as well as the release of morphine-6-g1ucuronide (14)(15). Finally, the highly potent effects of nicotine derived alkaloids found in brain tissues with weak binding activity for catecholamine receptors (19)(20)(21)(22), suggesting another function (22). Ethanol treatment increased THP levels in L-DOPA treated rat brains (23).…”

Alkaloids

“…This concept was shown by Nimit et al, 315 whereby series of benzylisoquinoline alkaloids were able to bind mainly to adrenergic receptor subtype β1, adrenergic receptor subtype ■ ■ FIGURE 1.9 Phellodendron amurense Rupr. This concept was shown by Nimit et al, 315 whereby series of benzylisoquinoline alkaloids were able to bind mainly to adrenergic receptor subtype β1, adrenergic receptor subtype ■ ■ FIGURE 1.9 Phellodendron amurense Rupr.…”

“…This concept was shown by Nimit et al, 315 whereby series of benzylisoquinoline alkaloids were able to bind mainly to adrenergic receptor subtype β1, adrenergic receptor subtype ■ ■ FIGURE 1.9 Phellodendron amurense Rupr. 315 Likewise, norreticuline and reticuline from Papaver somniferum L. (family Papaveraceae Juss. 315 Likewise, norreticuline and reticuline from Papaver somniferum L. (family Papaveraceae Juss.…”

“…1 μM, 2 μM, 6 μM, and 6.5 μM. 315 Reticuline, 6-methoxytetrahydropapaveroline, and tetrahydropapaveroline bind to adrenergic receptor subtype α2 with IC 50 values equal to 5 μM, 8 μM, and 8 μM, respectively. ), 6-methoxytetrahydropapaveroline, and 3′-methoxytetrahydropapaveroline bind D 2 with IC 50 values equal to 3 μM, 4.5 μM, 4.5 μM, and 5 μM, respectively.…”

“…315 Likewise, norreticuline and reticuline from Papaver somniferum L. (family Papaveraceae Juss. 315 6-Methoxytetrahydropapaveroline, reticuline, and norreticuline bind to serotoninergic receptors with IC 50 values equal to 10 μM. 315 Reticuline, 6-methoxytetrahydropapaveroline, and tetrahydropapaveroline bind to adrenergic receptor subtype α2 with IC 50 values equal to 5 μM, 8 μM, and 8 μM, respectively.…”