A Zindo/1 Study of the Cannabinoid-Mediated Inhibition of Adenylyl Cyclase

Abstract

We present here the results of a formal structure-property relationship study carried out for 1 CB - and 2 CB -mediated inhibition of adenylyl cyclase (ADC) by a group of classical cannabinoid derivatives. The wave function was calculated with Zerner’s ZINDO/1 method. Several reactivity indices were calculated from the wave function for a molecular skeleton common to all the molecules. Multiple regression analysis was employed to find the best equation for each case. We found that: (1). the variation of the the cannabinoid-mediated inhibition of ADC is related to the variation of a definite set of molecular reactivity indices, (2). the internal molecular orbitals are extremely important in regulating the cannabinoid-receptor interaction, and (3). the mechanism for the cannabinoid-mediated inhibition of ADC is different for each receptor, involving electrostatic interactions, electron transfer and geometrical substituent effects.