chapter  36
10 Pages

HU-211: A Cannabinoid Neuroprotective Agent

In 1988, in a study on the relationship between stereochemistry (structure in space) and cannabinoid activity, we prepared a highly potent analogue of t.8-THC-code numbered HU-210-as well as its enantiomer (mirror image)--code numbered HU-211 (see Figure 36.1).15,17 HU-210 proved to be the most potent cannabinoid synthesized until then. In various tests in vitro and in vivo, HU-210 was between 80 and 800 times more active than the natural t.9-THC, depending on the test employed.l4,16 In contrast, HU-211 did not show any THC-type activity when measured in numerous tests: it did not cause sedation, immobility, reduction of body temperature, etc., even when tested at doses several thousand times higher than the active doses of HU-210.14,16 However, on administration of relatively high doses of HU-211 to mice, we noted behavior-grooming, rearing, scratching, and licking-which resembled that of antagonists to the glutamate receptor (or more exactly, to the N=methyl D=asparate (NMDA) subtype of the glutamate receptor).8 Glutamate is the principal excitatory transmitter in the brain. It activates several receptor subtypes, one of which is named after the compound N-methyl, D-aspartic acid (NMDA) which activates a particular receptor SUbtype.