Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: KEGG:D05731 (Rimonabant)
 326 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The field of cannabinoid (CB) drug research is experiencing a challenge as the CB(1) antagonist Rimonabant, launched in 2006 as an anorectic/anti-obesity drug, was withdrawn from the European market due to the complications of suicide and depression as side effects. There is interest in developing CB(2) drugs without CB(1) psychotropic side effects for drug-abuse treatment and therapeutic medication. The CB(1) receptor was discovered predominantly in the brain, whereas the CB(2) is mainly expressed in peripheral cells and tissues, and is involved in immune signal transduction. Conversely, the CB(2) receptor was recently detected in the CNS, for example, in the microglial cells and the neurons. While the CB(2) neurons activity remains controversial, the CB(2) receptor is an attractive therapeutic target for neuropathic pain, immune system, cancer and osteoporosis without psychoactivity. This review addresses CB drug abuse and therapeutic potential with a focus on the most recent advances on new CB(2) ligands from the literature as well as patents.
 ...
PMID:Latest advances in novel cannabinoid CB(2) ligands for drug abuse and their therapeutic potential. 2230 98

The cannabinoid receptor subtype 2 (CB2) is a promising therapeutic target for blood cancer, pain relief, osteoporosis, and immune system disease. The recent withdrawal of Rimonabant, which targets another closely related cannabinoid receptor (CB1), accentuates the importance of selectivity for the development of CB2 ligands in order to minimize their effects on the CB1 receptor. In our previous study, LiCABEDS (Ligand Classifier of Adaptively Boosting Ensemble Decision Stumps) was reported as a generic ligand classification algorithm for the prediction of categorical molecular properties. Here, we report extension of the application of LiCABEDS to the modeling of cannabinoid ligand selectivity with molecular fingerprints as descriptors. The performance of LiCABEDS was systematically compared with another popular classification algorithm, support vector machine (SVM), according to prediction precision and recall rate. In addition, the examination of LiCABEDS models revealed the difference in structure diversity of CB1 and CB2 selective ligands. The structure determination from data mining could be useful for the design of novel cannabinoid lead compounds. More importantly, the potential of LiCABEDS was demonstrated through successful identification of newly synthesized CB2 selective compounds.
 ...
PMID:LiCABEDS II. Modeling of ligand selectivity for G-protein-coupled cannabinoid receptors. 2327 50

Osteoporosis is a common health problem. The endocannabinoid pathway has been implicated as an important regulator of bone turnover. Rimonabant is a potent cannabinoid receptor1 (CB1) receptor antagonist with wide therapeutic use as an antiobesity drug that has been withdrawn due to side effects in the form of depression and suicidal attacks. This study investigated whether glucocorticoid induced bone loss is linked to CB1 signaling and whether modulation of CB1 function affects the deleterious effects of glucocorticoid treatment on bone remodeling in rats. Sixty four rats were divided into two main groups: group 1 (G1) consisted of 12-14 month old rats and group 2 (G2) consisted of 3-4 month old rats. Each main group subdivided into four subgroups as follows: (NC1) and (NC2), the negative control groups, (MP1) and (MP2), received methylprednisolone (glucocorticoid), (RIM1) and (RIM2), received rimonabant, (MP + RIM1) and (MP + RIM2) received methylprednisolone with rimonabant. There was a significant decrease in bone mineral density (BMD) and bone mineral content (BMC) of the tibia bones together with a decrease in osteoprotegrin (OPG) expression but with a significant increase in receptor activator of nuclear factor kappa B ligand (RANKL) expression in osteoporotic rats. These parameters were reversed with co-administration of rimonabant with methylprednisolone in young rats, though it increased the severity of osteoporosis in older rats. Image analysis technique revealed that there was a significant improvement in cortical bone thickness (CBT) and mean trabecular bone density (TBD) in young group only after rimonabant either alone or with glucocorticoid. CB1 receptors play age related different roles in bone turnover. So, CB1 antagonist can be used to prevent corticosteroid induced osteoporosis in young age but should be avoided in old age.
...
PMID:Effect of cannabinoid receptors 1 modulation on osteoporosis in a rat model of different ages. 2537 28