Interaction of catecholamine-derived alkaloids with central neurotransmitter receptors

✍ Scribed by Y. Nimit; I. Schulze; J. L. Cashaw; S. Ruchirawat; V. E. Davis

• Publisher: John Wiley and Sons
• Year: 1983
• Tongue: English
• Weight: 919 KB
• Volume: 10
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.490100207

✦ Synopsis

Catecholamine-derived alkaloids of the simple tetrahydroisoquinoline, I -benzyltetrahydroisoquinoline 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 'H-clonidine binding to cq-adrenergic receptors. Stereoselectivity of tetrahydropapaveroline in binding to al-adrenergic receptors was evidenced by the marked activity of the S-( -) isomer (I& = 0.65 pM) in comparison to the R-(+) enantiomer (IC50 =, 50 pM). The simple tetrahydroisoquinolines (3,4-dihydroxytetrahydroisoquinoline and salsolinol), the four isomeric mono-0methyl derivatives of 2,3,10,1 I -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 'H-WB-4101 binding to al-adrenergic receptors. The l-benzyltetrahydroisoquinolines exhibited varying degrees of interaction with /3 -adrenergic receptors. Tetrahydropapaveroline (IC50 = 0.3 pM) was the most active of the 24 alkaloids tested in inhibiting binding of 'H-dihydroalprenolol to P1-adrenergic receptors. None of the alkaloids significantly affected 'H-QNB binding to muscarinic-cholinergic receptors, and selected alkaloids from each class interacted only moderately with serotonergic receptors.