Rutecarpine or rutaecarpine is a
COX-2 inhibitor
COX-2 inhibitors are a type of nonsteroidal anti-inflammatory drug (NSAID) that directly targets cyclooxygenase-2, COX-2, an enzyme responsible for inflammation and pain. Targeting selectivity for COX-2 reduces the risk of peptic ulceration and i ...
isolated from ''
Tetradium ruticarpum
''Tetradium ruticarpum'' is a tree that comes from China and Korea. It was previously classified in the genus '' Euodia'' as ''Euodia ruticarpa''. The fruit is usually used, denoted sometimes as ''fructus''. It has a strong bitter taste, and i ...
'', a tree native to China. It is classified as a non-basic
alkaloid
Alkaloids are a class of basic, naturally occurring organic compounds that contain at least one nitrogen atom. This group also includes some related compounds with neutral and even weakly acidic properties. Some synthetic compounds of similar ...
.
In contrast to synthetic COX-2 inhibitors like
etoricoxib
Etoricoxib, sold under the trade name Arcoxia, is a selective COX-2 inhibitor from McOLSON Research Laboratories. Currently it is approved in more than 80 countries worldwide but not in the US, where the Food and Drug Administration (FDA) has r ...
and
celecoxib
Celecoxib, sold under the brand name Celebrex among others, is a COX-2 inhibitor and nonsteroidal anti-inflammatory drug (NSAID). It is used to treat the pain and inflammation in osteoarthritis, acute pain in adults, rheumatoid arthritis, ankyl ...
, rutecarpine does not appear to cause negative effects on the
cardiovascular system
The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...
.
Metabolism
Microsome
In cell biology, microsomes are heterogeneous vesicle-like artifacts (~20-200 nm diameter) re-formed from pieces of the endoplasmic reticulum (ER) when eukaryotic cells are broken-up in the laboratory; microsomes are not present in healthy, livin ...
studies suggest that rutaecarpine may be at least a weak
inhibitor
Inhibitor or inhibition may refer to:
In biology
* Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity
* Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotra ...
of
CYP1A2
Cytochrome P450 1A2 (abbreviated CYP1A2), a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the human body. In humans, the CYP1A2 enzyme is encoded by the ''CYP1A2'' gene.
Function
...
,
CYP2C9
Cytochrome P450 family 2 subfamily C member 9 (abbreviated CYP2C9) is an enzyme protein. The enzyme is involved in metabolism, by oxidation, of both xenobiotics, including drugs, and endogenous compounds, including fatty acids. In humans, the prote ...
,
CYP2C19
Cytochrome P450 2C19 (abbreviated CYP2C19) is an enzyme protein. It is a member of the CYP2C subfamily of the cytochrome P450 mixed-function oxidase system. This subfamily includes enzymes that catalyze metabolism of xenobiotics, including some pr ...
,
CYP2E1
Cytochrome P450 2E1 (abbreviated CYP2E1, ) is a member of the cytochrome P450 mixed-function oxidase system, which is involved in the metabolism of xenobiotics in the body. This class of enzymes is divided up into a number of subcategories, includ ...
, and
CYP3A4
Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine. It oxidizes small foreign organic molecules (xenobiotics), such as toxins or drugs, so that they can be removed from t ...
enzymes. At the same time, it is believed to be a strong
inducer
In molecular biology, an inducer is a molecule that regulates gene expression. An inducer functions in two ways; namely:
*By disabling repressors. The gene is expressed because an inducer binds to the repressor. The binding of the inducer to the r ...
of
CYP1A2
Cytochrome P450 1A2 (abbreviated CYP1A2), a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the human body. In humans, the CYP1A2 enzyme is encoded by the ''CYP1A2'' gene.
Function
...
and
CYP1A1
Cytochrome P450, family 1, subfamily A, polypeptide 1 is a protein
that in humans is encoded by the ''CYP1A1'' gene.
The protein is a member of the cytochrome P450 superfamily of enzymes.
Function
Metabolism of xenobiotics and drugs
CYP1A1 ...
.
Rutecarpine metabolism is complex and proceeds along several routes, primarily involving the addition of a single
hydroxyl group
In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydroxy g ...
by
CYP3A4
Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine. It oxidizes small foreign organic molecules (xenobiotics), such as toxins or drugs, so that they can be removed from t ...
. Six monohydroxylated and four dihydroxylated
metabolite
In biochemistry, a metabolite is an intermediate or end product of metabolism.
The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...
s have been identified. To a much lesser extent, rutecarpine may be metabolized by
CYP2C9
Cytochrome P450 family 2 subfamily C member 9 (abbreviated CYP2C9) is an enzyme protein. The enzyme is involved in metabolism, by oxidation, of both xenobiotics, including drugs, and endogenous compounds, including fatty acids. In humans, the prote ...
and
CYP1A2
Cytochrome P450 1A2 (abbreviated CYP1A2), a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the human body. In humans, the CYP1A2 enzyme is encoded by the ''CYP1A2'' gene.
Function
...
, according to liver microsome studies.
Supplementation
Rutecarpine has been shown to decrease the overall
bioavailability
In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation.
By definition, when a medication is administered intravenously, its bioavailability is 100%. H ...
of
caffeine
Caffeine is a central nervous system (CNS) stimulant of the methylxanthine class. It is mainly used recreationally as a cognitive enhancer, increasing alertness and attentional performance. Caffeine acts by blocking binding of adenosine t ...
in rats by up to 80 percent, likely through induction of enzymes
CYP1A2
Cytochrome P450 1A2 (abbreviated CYP1A2), a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the human body. In humans, the CYP1A2 enzyme is encoded by the ''CYP1A2'' gene.
Function
...
and
CYP2E1
Cytochrome P450 2E1 (abbreviated CYP2E1, ) is a member of the cytochrome P450 mixed-function oxidase system, which is involved in the metabolism of xenobiotics in the body. This class of enzymes is divided up into a number of subcategories, includ ...
.
References
{{Prostanoidergics
COX-2 inhibitors
Indole alkaloids
Heterocyclic compounds with 5 rings
Ketones