Biomedical Engineering Reference
In-Depth Information
Sanoi -Aventis has a CB
1
-antagonist (SR141716A, Rimonabant, trade name Acomplia, refer to
Figure 19.12) on the European market for the treatment of obesity (body mass index above 30). Large
cl i n i c a l t r i a l s h ave s h ow n t h a t R i m o n a b a n t i n d u c e s a we ig h t l o s s o f ~10 % o f i n it i a l b o d y we ig h t w it h i n
1 year. The discontinuation of Rimonabant treatment results in the regain of lost weight. It is not
clear how large a fraction of the weight loss effect of rimonabant is mediated by CB
1
-receptors in
the CNS relative to CB
1
-receptors in the peripheral organs like the liver and adipose tissue. Side
effects are increased frequency of nausea and mood disturbances like depression. Rimonabant is
not approved in United States. A CB
1
-receptor antagonist that does not cross the blood-brain barrier
may possibly also have benei cial effects on energy metabolism.
Emerging evidence points to a possible participation of the endocannabinoid system in the regu-
lation of the relapsing phenomenon of drug abuse in animal models. CB
1
-receptor seems to be
important in drug as well as cue-induced reinstatement of drug seeking behavior. Stimulation may
elicit relapse not only to cannabinoid seeking but also to cocaine, heroin, alcohol, and metham-
phetamine, and this effect is signii cantly attenuated in animal experiments by pretreatment with
CB
1
-receptor antagonists.
Potential clinical application involves drugs that can increase or decrease endocannabinoid levels
(i.e., FAAH-inhibitors and monoacylglycerol-lipase inhibitors or diacylglycerol-lipase inhibitors,
respectively) or serve as agonists/antagonists for the two cannabinoid receptors (Table 19.3). Thus
the potential is large but so is also the risk for side effects since the endocannabinoid system appears
to be so ubiquitous.
TABLE 19.3
Potential Clinical Applications of the Endocannabinoid System
Therapeutic Target
Clinical Conditions
CB
1
-Agonists
CB
2
-Agonists
CB
1
-Antagonists
FAAH-Inhibitors
Alzheimer's disease
X
X
AIDS and Cancer
Appetite stimulation and inhibition of
nausea and vomiting
#
Cancer
Inhibition of growth, angiogenesis, and
metastasis
X
X
X
Inl ammatory bowel diseases
Stimulation of gastrointestinal mobility
and reduction of inl ammation
X
X
Multiple sclerosis
X
X
Inhibition of tremors and spasticity
Obesity X
X#
Weight loss
Osteoporosis
X#
X
Inhibition of bone loss
Parkinson's disease
X
Pain
Chronic, inl ammatory, and
neuropathic
X
X
X
Note:
X, based on preclinical data from corresponding animal models; #, based on data from human studies or clinical trial.
