Pain Testing Models TetraQ offers a range of techniques for investigating the effectiveness of potential pain drugs, with a focus on in vivo models. We are leaders in in vivo pain models and are continually expanding our offering to include new models. Cisplatin-induced Neuropathy in Rats Vehicle (n=5) Nociceptive Pain (validated) Gabapentin (50 mg/kg) (n=6) Gabapentin (100 mg/kg) (n=5) Tail flick & hotplate tests
•Behavioural endpoints: noxious thermal stimuli
–Highly predictive for strong opioid analgesics &
Formalin test •Model of persistent nociceptive pain
•Behavioural endpoints: licking, biting & flinching
Post-surgical pain model (Brennan model) •Behavioural endpoints: mechanical allodynia & hyperalgesia Other Rodent Pain Models (validated) Inflammatory Pain (validated) •FCA-rat model of inflammatory pain
•Behavioural endpoints: hyperalgesia & hindpaw
Capsaicin-induced hindpaw sensitivity •EAE-mouse model of neuropathic pain Multiple Models of Neuropathic Pain •Bone cancer pain (validated) •Behavioural endpoints: mechanical allodynia & Chronic Constriction Injury of the Sciatic Nerve
•Behavioural endpoints: allodynia & hyperalgesia
Painful Diabetic Neuropathy •Streptozotocin Other Rodent Models of Persistent Pain Currently in Development
•Behavioural endpoints: allodynia & hyperalgesia
Varicella zoster virus (VZV)-induced neuropathy ddC-induced Neuropathy
•Human VZV isolates currently being cultured
•Behavioural endpoints: mechanical allodynia &
•Behavioural endpoints: mechanical allodynia &
•Aim to have validation completed in Q3 2011
Chemotherapy (cisplatin)-induced Neuropathy •Behavioural endpoints: mechanical allodynia & hyperalgesia w w w . t e t r a q . c o m . a u June2011 TetraQ has experience with a variety of pain target classes and pain drug molecule classes. Additionally, TetraQ offers bioanalytical, toxicology and pharmaceutics capabilities in support of pain drug development. TetraQ Experience: ex vivo Assessments
•Real-time RT-PCR •Immunohistochemistry •Bioanalysis of plasma/CSF concentrations of test Quantitative Assessment of the Following Side-
compounds – systemic exposure; identify targeted
Effects in in vivo Studies in Rats:
therapeutic plasma concentration for subsequent clinical studies
•Respiratory depression in awake freely moving rats using
•Pharmacokinetics of test compounds
whole body plethysmography•Constipation in rats (castor oil test & charcoal test)
TetraQ Experience: Drug Target Classes
•Motor impairment (rotarod)•General activity (activity cage)
•GPCRs
-Opioids-Others – commercial-in-confidenceBioanalysis Services – ADME
•Transporters
•GLP recognised & NATA ISO 17025, Research &
-Norepinephrine transporter (Mr1A, Xen2174)
Development Accredited •Bioanalytical method development & sample analysis of
•Ion Channels
drugs/metabolites in biological fluids, human and animal
-N-type calcium channel blockers– (CVID, MVIIA)
- subunit of Ca2+-channel – (gabapentin)
-Others - commercial-in-confidence
•in vitro and in vivo bioavailability and pharmacokinetic studies
•Enzymes
•Drug metabolism studies including metabolite identification
-Kinases - commercial-in-confidence
•Biodistribution and plasma protein binding studies •Toxicokinetics
TetraQ Experience: Molecule Classes: Toxicology
•Small Molecules •Peptides •Proteins
• Genotoxicity assays (Ames Test, Micronucleus, Mouse
•siRNA
Lymphoma Assay)• In vivo acute & repeat dose (chronic) toxicity studies
Drug Dosing Routes in Rodents
• In vivo safety pharmacology (including hERG, respiratory and CNS)
•Oral (by gavage) •Intravenous •Intraperitoneal Pharmaceutics •Subcutaneous •Intrathecal & epidural •Intracerebroventricular & intracerebral •Intradermal –Parenteral routes –via injection or continuous infusion
• Stability trials & stability indicating method development
–Infusion –via Culex machine or osmotic mini-pump
Key Contacts: Senior Manager: Dr. Bruce Wyse
b.wyse@tetraq.com.au Business Manager: Otto Damsma w w w . t e t r a q . c o m . a u
Veuillez lire attentivement cette notice avant de prendre ce médicament. Elle contient des informations importantes pour votre • Ce médicament peut être utilisé en automédication, c’est-à-dire utilisé sans consultation ni prescription d’un médecin. • Si les symptômes persistent, s’ils s’aggravent après 2 jours de traitement ou si de nouveaux symptômes apparaissen
Chapter 5 Quiz Review November 19, 2008 Answer questions on another sheet of paper. 1. Canada requires that cars be equipped with “daytime running lights,” headlights that automatically come on at a low level when the car is started. Many manufacturers are now equipping cars sold in the United States with running lights. Will running lights reduce accidents by making cars more visible?