1. By: Nick Giron Angela Shaw Victor Salayandia Agustin Salcido
Prialt
By:
Nick Giron
Angela Shaw
Victor Salayandia
Agustin Salcido

2. Why Prialt Interest in naturally occurring drugs
Huge potential for other drugs to come from the genus, conus
Very effective drug non-opioid pain reliever, that is none addictive.

3. Introduction Why research Conus magus and ω-conotoxin peptide?
Fascinating creature that produces therapeutically beneficial pain-relieving toxin

4. Intro (cont.) Genus Genus: Conus
Large genus comprising over 600 species
Reside in warm, tropical marine environments throughout the world
Common in small pacific islands especially in the Philippines
Habitat is coral reefs
Predatory marine gastropod mollusks (sea snails)
Its predators are crabs and other crustaceans
cone snail hunting

5. Intro (cont.) Genus Genus: Conus (cont.)
Hunt and consume small fish, marine worms, mollusks, and other cone snails
Use a hook-and-line method
Engulfs prey after it has been paralyzed by its venom.
Shell Pattern
Extremely variable and will look different depending on which island they are found.
All cone snails are venomous
Move at a "snail's pace," half a millimeter per second, evolved the ability to produce and deliver paralytic venom to capture prey
Siphon: sensory organ used to detect prey
Venom delivery: Hypodermic-like radula made of chitin and coated in venom at the end of a proboscis that can be extended from the mouth
No anti-venom available at this time.
There are 15 reported death contributed to cone snail envenomation’s. stings most commonly occur when the cone snail are picked up.

6. What is a toxin
A toxin is a substance produced by an organism with adverse affects on another organism
Can be deffensive
Can be offensive
A Small molecule, peptide, or protein that can cause disease

7. Conotoxins
Characteristics: disulfide rich peptides amino acids in length with high specificity to ion channel receptors and transporters in nervous system

8. Conotoxin (cont.)

9. Conotoxicity signs and symptoms
Non-fatal cases include:
Burning pain
Swollen arm and pain
Local numbness spreading rapidly to involve the entire body with some cardiac and respiratory distress
Progressive weakness, loss of coordination, drooping eyelids, shallow breathing
Headache, nausea, stomach cramps, shortness of breath

10. Conotoxicity signs and symptoms (cont.)
Fatal Cases include:
These symptoms occur almost immediately upon injection
Numbness without pain (some species produce severe pain and spreading numbness)
Lips become stiff
Blurred vision
Paralysis
Coma
Death occurs as the result of respiratory and/or cardiovascular collapse. (

11. Pharmacological families
Family
α (alpha)
Nicotinic acetylcholine receptors (nAChR)
γ (gamma)
Neuronal pacemaker cation currents (inward cation current)
δ (delta)
Voltage-gated Na channels (agonist, delay inactivation)
ε (epsilon)
Presynaptic Ca channels or G protein-coupled presynaptic receptors
ι (iota)
Voltage-gated Na channels (agonist, no delayed inactivation)
κ (kappa)
Voltage-gated K channels (blocker)
μ (mu)
Voltage-gated Na channels (antagonist, blocker)
ρ (rho)
Alpha1-adrenoceptors (GPCR)
σ (sigma)
Serotonin-gated ion channels (GPCR)
χ (chi)
Neuronal noradrenaline transporter
ω (omega)
Voltage-gated Ca channels (blocker)

12. ω-conotoxin peptide from Conus magus
Discovered in late 1960s by Baldomero Olivera during his postdoc work at Stanford University
Peptide that consist of 10 to 30 amino acids

13. Mechanism
blocks N-type voltage-gated calcium channels which are involved in analgesia (pain sensitivity)

14. Administration
administration through oral and intravenous routes often have severe adverse effects
Intrathecal pump system is the safest way for delivery
This carries additional risk such as infection.
Used in chronic pain suffering patients

15. Uses for Prialt Bioterrorism Chronic pain Failed back surgery
Multiple sclerosis
Neuropathy
Cancer
AIDS

16. Side effects
“Abnormal walking; back pain; bad taste in mouth; burning, aching, tingling sensation on the skin; constipation; diarrhea; dizziness; dry skin; feeling of a whirling motion; incoordination; increased cough; loss of appetite; muscle tension; pain; pain at insertion site; rapid, jerky eye movements; ringing in the ears; runny nose; skin irritation; sleepiness; sore throat; stomach pain; sweating; vision changes.” (

17. Side effects (cont.) 33% reported confusion
22% reported memory impairment
14% reported Speech disorder
12% reported aphasia
8% reported abnormal thinking
1% reported amnesia
Cognitive impairment may appear after several weeks

18. Severe side effects
If the following reaction occur, doctors advise immediate medical help:
“ Severe allergic reactions (rash; hives; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); abnormal thinking; anxiety; change in mental state (eg, lack of energy, confusion, disorientation); change in mood or perception (eg, hallucinations; unusual sensations in the mouth; paranoia; hostility; delirium; manic reactions; psychosis); chest pain; dark urine; depression; fainting; fever; flu-like symptoms; headache; inability to empty the bladder; memory problems or memory loss; muscle cramps; muscle or joint pain; nausea; nervousness; pounding in the chest; seizures; speech problems; stiff neck; stupor; suicidal thoughts or behaviors; unresponsiveness; urination problems; vomiting; weakness.” (

19. Metabolism
Following intrathecal administration, Prialt is rapidly distributed and metabolized in the spinal cerebrospinal fluid
Followed by rapid mass transport from the CSF to the plasma

20. Drug-drug interaction
Can interact with:
anti-seizure medication
Antihistamine
Sleep or anxiety medication
Narcotic pain relievers
Muscle relaxants
Psychiatric

21. Further research on Conus
With over 600 species of conus snail, there is huge promise for many other new medications.
ACV1 is one example and is entering phase 2 testing
Potentially times more potent than morphine.
Potentially can repair injured nerves which is unique for an analgesic

22. Literature cited
grimwade.biochem.unimelb.edu.au/cone/