pharmacology of cannabinoid

PHARMACOLOGY OF CANNABINOID RECEPTORS

PRESENTED BY RAJEEV MISHRA 2ND SEM M-PHARMACY PHARMACOLOGY

Cannabinoids are a group of chemicals which activate the bodyrsquos cannabinoid receptors

There are three general types of cannabinoids

Endogenous cannabinoids produced in the bodies of humans and otheranimals1048766

Herbal cannabinoidspresent in the Cannabis plant

Synthetic cannabinoids similar compounds produced in a laboratory

CANNABINOIDS

Cannabinoid receptors are part of the endocannabinoid system which consists of cannabinoid receptor endogenous cannabinoids (endocannabinoids) and the enzymes that synthesis and degrade endocannabinoids

The cannabinoid receptors are a class of cell membrane receptors under the G protein-coupled receptor superfamily

Cannabinoid receptors are activated by three major group of ligands endocannabinoids plant cannabinoids lsquolsquosynthetic cannabinoids

All of the endocannabinoids and plant cannabinoids are lipophilic ie fat soluble compounds

Cannabinoid receptors

TYPES OF CANNABINOID RECEPTORS

There are currently two known subtypes termed CB1 and CB2

Several endogenous cannabinoids have been identified and the synthetic and degradative pathways of the endocannabinoids have been partially elucidated

Both CB1 and CB2 receptors belong to the superfamily of G protein-coupled receptors coupling to inhibitory G proteins (Gio)

The CB1 receptor was first cloned as orphan receptor from a rat cDNA library

Mainly expressed in BRAIN (CNS) LIVER LUNGS KIDNEY ON MALE FEMALE REPRODUTIVE SYSTEM

BRAIN region- basal ganglia limbic system hippocampus cerebellum involved with thinking amp memoryattention movement controlIn addition CB1 receptors inhibits presynaptic N- and PQ-type calcium channels and activate inwardly rectifying potassium channels

CB1 RECEPTOR

CB2 receptors are mainly expressed ion T CELSS of immune system on B CELLS on MACROPHAGESon HEMATOPOIETIC CELLS

ALSO expressed on peripheral nerve terminal

IN BRAINexpressed by microglial cells

HAVE function as KERATINOCYTESampplay a role in NOCICEPTION (percepion of pain )

CB2 RECEPTOR

CANNABINOID FROM PLANT

Plant cannabinoids are obtained from plant CANNABISIn species- csativacindica

CANNABIS also known as HEMPAs a drug it usually comes in the form of dried flowers (marijuana) resin (hashish) or various extracts collectively referred to as hash oil

Cannabis has been used by different civilizations for a variety of medical applications such as pain stimulation of appetite nausea fever infections and gynecological disorders

Endogenous cannabinoids

Two families of endogenous cannabinoids are known

Endocannabinoids are eicosanoids acting as agonists for cannabinoid receptors and they occur naturally in the body The first identified was anandamide (arachidonoyl ethanolamide) and the second was 2-AG (2-arachidonoyl glycerol) Additional endocannabinoids include virodhamine (O-arachidonoyl ethanolamine) noladin ether (2-arachidonoyl glyceryl ether) and NADA (N-arachidonoyl dopamine)

The endogenous cannabinoid system amp their signalling

The endogenous cannabinoid system includes cannabinoid receptors their endogenous ligands (endocannabinoids) and enzymes for their synthesis and degradationThere are two main receptor types associated with the endocannabinoid signaling system cannabinoid receptor 1 (CB1) and 2 (CB2) Both receptors are 7-transmembrane G-protein coupled receptors (GPCRs) which inhibit the accumulation of cyclic adenosine monophosphate within cells Endocannabinoid mediated inhibition of neurotransmission comes in two forms transient and long lasting

long-term depression (LTD) LONG LASTING

TransientDSI(depolarization-induced suppression of inhibition) or DSE (depolarization-induced suppression of excitation)

CB1 Receptor agonist

Endocannbinoids are agonist for cb1 receptorsANANDAMIDE amp 2-AG are two endocannabinoid located in brain

Anandamide ndash 1st endogenous cannbinoid from porcine brainHave functions mesentric vasodilation in vivo amp PSHYCOACTIVE EFFECThave low efficacy (agonist action ) at cb1 receptor similar to delta9 THC

Degrades by FAAH (fatty acid amino hydrolase )

2mdashAG (2-ARACIDNOYL GLYCEROL ) 2ND AFTER ANANDAMIDEmajor highly effective attenuates the early phase amp late phase behaviour amp produce endothelium induced hypotension

Degrades by MAG LIPASE (mono glycerol lipase )

CB2R selectiveagonists

CB2 receptor agonists have potentially useful effects in a number of models of inflammatory and neuropathic pain possibly involving the release of endogenous opioids and can inhibit growth of CB2-receptor-expressing gliomain vivo

Cb2 agonist useful in various model for osteoporosis artherosclerosis

clinical studies suggest that CB1 antagonists have significant metabolic effects that extend beyond decreasing caloric intake

Rimonabant also known as SR141716 or Acompliareg was the first CB1 antagonist reported

It is a diarylpyrazole with nanomolar affinity for CB1 receptors and little affinity for the CB2 receptors

Many congeners of rimonabant have been synthesized and an SAR developed

CB1 Receptor Antagonists

Cb1 antagonist useful in smoking cessation appetite suppressent decrease food consumption obesity treatment

Cannabinoids potential anticancer agents

It is commonly assumed - although not rigorously proven that endocannabinoid action is terminated in part by their uptake into cells

This putative mechanism appears similar for anandamide and 2-AG with some mild difference

However whether endocannabinoid transport occurs through a specific transporter or by nonspecific means is still the subject of some debate

The initial pharmacological probe used to study the putative endocannabinoid membrane transporter (EMT) AM404 inhibited uptake but it also interacted with CB1 receptors and activated VR1 channels at higher concentrations

Endocannabinoid Transport Inhibitors

FAAH seems to be the major degradative enzyme for anandamide and related amides in vivoThus drugs that selectively inhibit FAAH would increase N-acylethanolamine levels without affecting those of 2-AGEg URB532 URB597 the reversible alpha-ketoheterocycle FAAH inhibitors are OL92

Fatty Acid Amino Hydrolase (FAAH )

Therapeutic Promises

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Cannabinoids are a group of chemicals which activate the bodyrsquos cannabinoid receptors

There are three general types of cannabinoids

Endogenous cannabinoids produced in the bodies of humans and otheranimals1048766

Herbal cannabinoidspresent in the Cannabis plant

Synthetic cannabinoids similar compounds produced in a laboratory

CANNABINOIDS













CB1 RECEPTOR





CB2 RECEPTOR




































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CB1 RECEPTOR





CB2 RECEPTOR




































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CB2 RECEPTOR




































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pharmacology of cannabinoid

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