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					                 Usi innovativi di farmaci antichi
L'attuale rivalutazione medica della Cannabis e dei cannabinoidi




          Cannabis e glaucoma

                    Dott.ssa Anna Porcella
        Istituto di Neurogenetica e Neurofarmacologia
          Consiglio Nazionale delle Ricerche, Cagliari
              Roma 6 ottobre 2001
          UNIVERSITÀ "LA SAPIENZA"
             Glaucoma
A condition of the eye where the
intraocular pressure is elevated beyond the
limit that will permit normal function of
the optic nerve.

 Almost 100 million people affected
    world wide
 7 million totally blind due to the
    progression of their glaucomas
PRIMARY OPEN ANGLE GLAUCOMA
           (POAG)

                         Open anterior
                         chamber




 The obstruction of the trabecular
 meshwork – Schlemm’s canal system
 blocks the outflow of aqueous humor
OUTFLOW OF AQUEOUS HUMOR
Marijuana smoking was first reported to reduce
intraocular pressure (IOP) in 1971 (Hepler and
Frank, 1971)

Cloning of CB1 and CB2 receptors and the
discovery of Endocannabinoids has opened the
field for research into their physiological roles

Distribution studies in both
the brain and the periphery
have shown that in some
tissues these receptors are
colocalized
 DIAGRAMMATIC CROSS SECTION
 OF THE ANTERIOR CHAMBER
                               ANTERIOR CHAMBER

            CORNEA




SCHLEMM’S CANAL
     SYSTEM                                          IRIS



SCLERA




                     CILIARY MUSCLE
                                                     LENS

                                      CILIARY BODY
CB1 mRNA IN THE RAT EYE
           Porcella et al. Mol. Br. Res, 1998
CB1 mRNA IN THE HUMAN EYE




           Porcella et al. Eur. J. Neurosci, 2000
CB1 PROTEIN IN THE HUMAN EYE




             Porcella et al. Eur. J. Neurosci, 2000
ARMAMENTARIUM OF DRUGS IN
  USE TO TREAT GLAUCOMA
a2 Adrenoreceptor agonists
b2 Adrenoreceptor antagonists
Prostaglandin Agonist
Dopamninergic agonist           Cannabinoids ?
Cholinergic Agonist
Carbonic Anhydrase Inhibitors
Guanylate Cyclase Activators
Adenosine agonist
NMDA Antagonist
        Natural cannabinoids


                           8-tetrahydrocannabinol
   9-THC




Cannabinol                          Cannabidiol


              Endogenous cannabinoids


 Anandamide                          2-AG
               Synthetic cannabinoids

Nabilone
                                             WIN 55,212-2


CP 55,940                                          HU 210



                                        LY320135
SR141716A



Palmitoyl-EA
                                               SR144528
 (CB2 only)
                ANIMAL        ROUTE OF   EFFECT ON
   DRUG                                               REFERENCE
                MODEL          ADMIN        IOP

               Normotensive
    AEA
                 rabbits    EYE DROPS                 Pate et al, 1996

               Normotensive
WIN-55,212-2                                         Hodges et al, 1997
                 rabbits        I.V.       NONE

               Normotensive
  CP-55,940      rabbits    EYE DROPS                 Pate et al, 1998

               Normotensive
WIN-55,212-2     rabbits    EYE DROPS                   Song, 2000
  8-THC
  9-THC   Normotensive
                                                       Elsohly, 1981
CANNABINOL   rabbits            I.V.
 NABILONE
 EFFECT OF TOPIC WIN55212-2 ON
IOP OF GLAUCOMATOUS PATIENTS




              Porcella et al. Eur. J. Neurosci, 2001
             SUMMARY (1)
THE HIGH LEVEL OF CB1 mRNA AND PROTEIN IN THE
CILIARY BODY SUGGEST A LOCALIZED VASODILATION BY
CANNABINOIDS

IN ADDITION INHIBITION OF PRESYNAPTIC Ca++
CHANNELS   BY    CANNABINOIDS MAY  REDUCE
NORADRENALINE RELEASE IN THE EYE AND THE
PRODUCTION OF AQUEOUS HUMOR

SR141716A ANTAGONIZES IOP LOWERING EFFECTS OF
CANNABINOIDS IN RABBITS SUGGESTING A DIRECT CB1
INVOLVEMENT IN THIS MECHANISM

HOWEVER THE MECHANISM BY WHICH CANNABINOIDS
ARE ABLE TO DECREASE IOP REMAINS TO BE FURTHER
ELUCIDATED
            SUMMARY (2)
IOP LOWERING EFFECTS OF TOPIC WIN55212-2 IN
GLAUCOMATOUS PATIENTS ARE TIME AND DOSE
DEPENDENT

SYNTHETIC CB1 AGONISTS SHOULD DESERVE
FURTHER RESEARCH AND CLINICAL DEVELOPMENT

				
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posted:8/30/2011
language:Italian
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