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[½»Á÷] Ôõô·­Òë°¡ÇóÖú£¬JBT-101ÊÇʲôÇó¸æÖª

abstract
Ajulemic acid, a side-chain analog of D8
-THC-11-oic acid, was designed as a potent therapeutic agent free
of the psychotropic adverse effects typical of most cannabinoids. Subsequent studies of ajulemic acid
have yielded widely divergent findings on the occurrence of these adverse effects. To help resolve these
discrepancies, we have prepared highly purified ajulemic acid using a different synthetic method than
previously reported in the literature and compared its cannabinoid receptor binding constants with those
obtained using several other preparations from different sources. Whereas CB2 binding did not vary
greatly among all of the samples, the CB1 binding showed a wide range of affinities. The highly purified
product (JBT-101) reported here had the weakest affinity for CB1 while the original preparation (HU-239)
showed the strongest affinity for CB1. The CB1/CB2 ratio of affinities was 12.3 for JBT-101 whereas that
for HU-239 was 0.19, a 65-fold difference. Functional responses such as catalepsy and hypothermia using
JBT-101 versus HU-239 displayed reduced CB1 activity in keeping with the receptor binding data. Thus,
earlier conclusions on the limited therapeutic index for ajulemic acid need to be reconsidered in the light
of the data now obtained using JBT-101.

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²ÊºçÌǵÄÃØÃÜ

гæ (СÓÐÃûÆø)

abstract
Ajulemic acid, a side-chain analog of D8
-THC-11-oic acid, was designed as a potent therapeutic agent free
of the psychotropic adverse effects typical of most cannabinoids. Subsequent studies of ajulemic acid
have yielded widely divergent findings on the occurrence of these adverse effects. To help resolve these
discrepancies, we have prepared highly purified ajulemic acid using a different synthetic method than
previously reported in the literature and compared its cannabinoid receptor binding constants with those
obtained using several other preparations from different sources. Whereas CB2 binding did not vary
greatly among all of the samples, the CB1 binding showed a wide range of affinities. The highly purified
product (JBT-101) reported here had the weakest affinity for CB1 while the original preparation (HU-239)
showed the strongest affinity for CB1. The CB1/CB2 ratio of affinities was 12.3 for JBT-101 whereas that
for HU-239 was 0.19, a 65-fold difference. Functional responses such as catalepsy and hypothermia using
JBT-101 versus HU-239 displayed reduced CB1 activity in keeping with the receptor binding data. Thus,
earlier conclusions on the limited therapeutic index for ajulemic acid need to be reconsidered in the light
of the data now obtained using JBT-101.

·¢×ÔСľ³æAndroid¿Í»§¶Ë
2Â¥2017-02-07 10:27:37
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