pharmacology of cannabinoid


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pharmacologgy of cannabinoid receptors

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pharmacology of cannabinoid

  2. 2.  Cannabinoids are a group of chemicals which activate the body’s cannabinoid receptors. There are three general types of cannabinoids: Endogenous cannabinoids produced in the bodies of humans and otheranimals􀂾 Herbal cannabinoids present in the Cannabis plant Synthetic cannabinoids similar compounds produced in a laboratory CANNABINOIDS ;;
  3. 3. 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;; ‘‘synthetic cannabinoids . All of the endocannabinoids and plant cannabinoids are lipophilic, i.e. fat soluble, compounds. Cannabinoid receptors ;;
  4. 4. 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 (Gi/o).
  5. 5. 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 & memory,attention , movement control} In addition, CB1 receptors inhibits presynaptic N- and P/Q- type calcium channels and activate inwardly rectifying potassium channels. CB1 RECEPTOR ;;
  6. 6. CB2 receptors are mainly expressed ion ;;; T CELSS of immune system;; on B CELLS;; on MACROPHAGES;;on HEMATOPOIETIC CELLS . ALSO expressed on peripheral nerve terminal . IN BRAIN;;expressed by microglial cells . HAVE function as;; KERATINOCYTES;&;play a role in NOCICEPTION (percepion of pain ) CB2 RECEPTOR ;;
  7. 7. CANNABINOID FROM PLANT ;; Plant cannabinoids are obtained from plant CANNABIS In species- c.sativa;;;;c.indica CANNABIS also known as HEMP;; As 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
  8. 8. 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).
  9. 9. The endogenous cannabinoid system & their signalling The endogenous cannabinoid system includes cannabinoid receptors, their endogenous ligands (endocannabinoids) and enzymes for their synthesis and degradation There 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 Transient;;DSI(depolarization-induced suppression of inhibition) or DSE (depolarization-induced suppression of excitation)
  10. 10. CB1 Receptor agonist Endocannbinoids are agonist for cb1 receptors. ANANDAMIDE & 2-AG are two endocannabinoid located in brain Anandamide – 1st endogenous cannbinoid from porcine brain Have functions mesentric vasodilation in vivo & PSHYCOACTIVE EFFECT;;have low efficacy (agonist action ) at cb1 receptor similar to delta9 THC. Degrades by FAAH (fatty acid amino hydrolase ) 2—AG (2-ARACIDNOYL GLYCEROL ) 2ND AFTER ANANDAMIDE;;major highly effective attenuates the early phase & late phase behaviour & produce endothelium induced hypotension. Degrades by MAG LIPASE (mono glycerol lipase )
  11. 11. 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;;
  12. 12.  clinical studies suggest that CB1 antagonists have significant metabolic effects that extend beyond decreasing caloric intake.  Rimonabant, also known as SR141716 or Acomplia®, 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
  13. 13. Cannabinoids: potential anticancer agents
  14. 14.  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
  15. 15. FAAH seems to be the major degradative enzyme for anandamide and related amides in vivo. Thus, drugs that selectively inhibit FAAH would increase N- acylethanolamine levels without affecting those of 2-AG. Eg; URB532, URB597 the reversible alpha-ketoheterocycle FAAH inhibitors are OL92 Fatty Acid Amino Hydrolase (FAAH )
  16. 16. Therapeutic Promises ;;
  17. 17. Thank uuuuuuuuu