Drugs that activate Gio-proteins receptors Domina Petric, MD

Opioids μ opioid receptors agonists cause euphoria. 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 inhibitory G-proteins (all of them inhibit adenylate cyclase). μ opioid receptors are in the VTA (ventral tegmental area) selectively present 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.

Abstinence syndrome can be very severe: 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

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 transmitters because they are released on the postsynaptic membrane and affect on the presynaptic CB1 receptors. When they bind on the CB1 receptors, they inhibit glutamate or GABA release. In the hippocampus endogenous cannabinoids release from pyramidal cells selectively affect on the inhibitory transmission and can be important for induction of synaptic plasticity during learning and memorising processes.

Cannabinoids THC is strong psychoactive drug. Exogenous cannabinoid that is very often abused is tetrahydrocannabinol (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 after several minutes and the maximum effects is after 1-2 hours.

THC effects euphoria relaxation disturbed perception of time memory disturbances sleepiness visual hallucinations depersonalisation psychotic episodes increased apetite nausea decreased intraocular pressure chronic pain release Potential for medical use!

It is usually mild and short lasting: 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 of colors and shapes. They can also induce psychotic symptoms like depersonalisation, hallucinations and distortion of time perception. These drugs also cause somatic symptoms like nausea, dizziness, paresthesia and blurred vision. Some of the hallucinogenic drugs abusers can experience flashbacks even years after last drug intake.

Hallucinogenic drugs Hallucinogenic drugs do not cause addiction, but they cause very fast tolerance (tachyphylaxis). Hallucinogenics do not activate mesolimbic dopaminergic system like most 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 bind with Gq-proteins and create inositol triphosphate (IP3) that causes release of intracellular calcium.

Katzung, Masters, Trevor. Clinical pharmacology.