6. Explain the neuropharmacology of heroin, marijuana, or opioids. . Your descri

Question

6. Explain the neuropharmacology of heroin, marijuana, or opioids. . Your description does not need to include 100% of lecture material. Include 1-2 strong examples from assigned reading to support your answer. a. What is thebiochemistry of the drug? b. What is the basic pharmacokinetics? c. What areas of the brain are involved? d. What NT's, stimuli, ligands and corresponding receptors transmit signs? e. What is the basic signalingpathway (EPSPs? IPSPs?) f. What are pathologies associated with system? g What are treatment options?

Explanation / Answer

Neuropharmacology involves that i) how a particular drug effects the cells of the nervous system i.e. how a drug interacts with the neurons and ii) what kind of mechanisms are involved when the drug starts manipulating the behaviour of an individual.

The neuropharmacology of opioids under various sections is as follows:

a) Biochemistry: Opioids are known to effect the i) dopamine mediated reward pathway (which causes the feeling of pleasure) and ii) the pain relieving pathway in the central nervous system.

b) Pharmacokinetics: Opioids are taken orally, dermally or epidermally as well as directly in the vein. The most effective being directly in vein as half of the amount reaches the CNS if administered in form of a pill. The metabolism occurs in liver by glucuridination mediated by the enzyme UDP-glucuranosyl transferase to form morphine-3-glucuronide and morphine-6-glucuronide. Morphine-6-glucuronide acts on to the receptors in brain and causes the nalagesic effects while the other metabolite is non binding in nature. The elimination occurs in about 72 hours by urination. Heroin is also metabolised in similar way but can cross the blood brain barrier easily and is converted to morphine in the brain.

c) Areas of brain involved: The areas of brain involved depend on the pathway. In case of reward pathway, the effect takes place on the cerebral cortex, ventral tegmental area and nucleus accumbens. In these areas it can creates the feeling of pleasure. For the analgesic pathway brain stem, thalamus and spinal cord are involved.

d) NT's , stimuli, ligands and receptor transmit signs: The neurotransmitters involved are Dopamine and GABA. various receptors like delta, kappa and mu etc are known while the mu receptors are mostly involved. The opiates (ligands) get attached to the opiate i.e mu receptors which are G-protein coupled receptors on the post synaptic neurons and signals the dopamine receptors to increase dopamine and hence causes the feeling of pleasure.

The GABAnergic receptors are put off by G-protein coupling. When opioids bind to receptors, then the G protien dissociates to G-alpha and G-betagamma subunits. G-betagamma subunit binds to voltage gated dependent calcium gated channels and causes hyperpolaraization. This prevents the release of substance P and glutamate from presynaptic neuron which are essential for transmission of pain and hence the analgesic effect takes place.

e) Basic signalling pathway: Opioids follow IPSP i.e the Inhibitory postsynaptic potential pathway as they cause disinhibition in dopamine neurons.

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