Drugs that activate inhibitory g proteins receptors
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Transcript of Drugs that activate inhibitory g proteins receptors
Domina Petric, MD
Drugs that activate Gio-proteins receptors
Opioids• Opioids are endogenous and exogenous agonists of three types of opioid
receptors: μ, κ and δ opioid receptors.
• All of these three types of receptors are associated with inhibitoryG-proteins (all of them inhibit adenylate cyclase).
• μ opioid receptors are in the VTA (ventral tegmental area) selectivelypresent on GABA neurons (which they inhibit).
• μ opioid receptors agonists cause euphoria.• κ opioid receptors are present on dopaminergic neurons (so they inhibit
those neurons).
• κ opioid receptors agonists cause dysphoria.
Opioids
• The most common abuse substances are μ opioids MORPHINE, HEROINE, CODEINE and OXYCODONE.
• All of these drugs cause severe tolerance and physical addiction.
Abstinence syndrome can be very severe:
• severe dysphoria
• nausea and vomit
• rhinorrhea
• mydriasis
• piloerection
• excessive sweating
• diarrhea
• fever
Treatment
Naloxone is opioid antagonist.
It is used for acute treatment.
For chronic opioids abuse treatment are used opioids with long lasting effect like
METHADONE and BUPRENORPHINE.
Cannabinoids
• Endogenous cannabinoids are neurotransmitters:
2-arachidonoylglycerol (2-AG) and anandamide.
• Endogenous cannabionids are called retrograde transmittersbecause they are released on the postsynaptic membrane and affect on the presynaptic CB1 receptors.
• When they bind on the CB1 receptors, they inhibit glutamateor GABA release.
• In the hippocampus endogenous cannabinoids release frompyramidal cells selectively affect on the inhibitorytransmission and can be important for induction of synapticplasticity during learning and memorising processes.
Cannabinoids
• Exogenous cannabinoid that is very often abused istetrahydrocannabinol (THC).
• THC is strong psychoactive drug.• THC causes disinhibition of dopaminergic neurons, especially
by presynaptic inhibition of GABA neurons in VTA.
• Half life of THC is 4 hours.
• Effect of THC after smoking starts afterseveral minutes and the maximum effects is after 1-2 hours.
THC effects
• euphoria
• relaxation
• disturbed perceptionof time
• memory disturbances
• sleepiness
• visual hallucinations
• depersonalisation
• psychotic episodes
increased apetite
nausea
decreased intraocularpressure
chronic pain release
Potential for medical use!
Abstinence syndrome
It is usually mild and short lasting:
Nausea
• Agitation
• Cramps
• Iritability
• Insomnia
GHB
γ-Hydroxybutyric acid (GHB) can be endogenous and exogenous.
Endogenous GHB is produced during GABA metabolism.
Exogenous GHB, if abused, causes euphoria, increased sensoric perception, feeling of
social intimacy and amnesia.
GHB is used as DRUG FOR RAPE.
Hallucinogenic drugs
• LSD, mescalin and psilocybe are hallucinogenic drugs.
• They induce perceptional symptoms like distortion ofcolors and shapes.
• They can also induce psychotic symptoms like
depersonalisation, hallucinations and distortion oftime perception.
• These drugs also cause somatic symptoms like nausea, dizziness, paresthesia and blurred vision.
• Some of the hallucinogenic drugs abusers can experienceflashbacks even years after last drug intake.
Hallucinogenic drugs
• Hallucinogenic drugs do not cause addiction, but they cause very fasttolerance (tachyphylaxis).
• Hallucinogenics do not activate mesolimbic dopaminergic system likemost other drugs do.
• Instead they increase glutamate release in the cortex.
• LSD is ergot alkaloid and it is neurotoxic.
• Onset of psychoactive LSD effects is after 30 minutes and lasts 6-12 hours.
• LSD can cause spontaneous abortion.
• Main molecular target of hallucinogenics is 5-HT2A receptors that bindwith Gq-proteins and create inositol triphosphate (IP3) that causesrelease of intracellular calcium.