Early safety profile: a complementary approach for lead selection

ANS Biotech provides its clients with a variety of early safety assessment services performed by a highly skilled team.

The Irwin observation test is commonly used to evaluate the effects of a new substance on behavior and physiological functions. This method described by Irwin in 1968 is part of the safety pharmacology core battery and is used to determine untoward effects of a new compound on general behavior, for evaluating its acute toxicity and selecting doses for specific therapeutic activity. The Irwin test can also furnish a first but pertinent orientation towards a specific therapeutic indication, a specific mechanism of action, or a specific physiological function.
The modified Irwin test enables a qualitative assessment of gross behavioral and physiological changes by systematically recording and ranking changes from normal on a score sheet. The test consists of 38 endpoints representing a series of subjective and quantitative measures on different aspects of nervous system function.

Behavioral and neurophysiological observations
 – Rats & Mice

Technical data sheet

The gastrointestinal tract (GI tract), which extracts nutrients, electrolytes, minerals, and water, is prone to dysfunction as a result of oral drug administration. To study the potential side effect of a candidate compound on gastrointestinal motility, the passage of charcoal meal through the gastrointestinal tract is a simple, reliable and widely used method in safety pharmacology.
The Charcoal meal test can be used for evaluation of laxative activity as well as for inhibition of motility encountered for a number of widely used analgesics such as Morphine. Assessment of GI transit is typically addressed by measurement of transit time and this method has been widely investigated by dosing rodents with an aqueous suspension of charcoal.

Charcoal meal test – Rats

Technical data sheet

Pain is a major social issue requiring the continuous development of new analgesics. With a lack of effective and safe non opioid options for pain management, the use of drugs with opioid based mechanisms of action remains widespread and is associated with numerous adverse effects, including a high risk of substance abuse in some people. Opioid misuse has developed in recent years, leading to a public health crisis. When taken in the prescribed quantities and for a short duration, opioids do not usually result in serious health complications, but their use to excess, compulsive intake or prolonged self-administration can lead, among other issues, to tolerance. The Morphine induced tolerance assay is widely used for revealing the potency of a new chemical entity to induce a tolerance phenomenon in conscious rats.

Tail flick test – Rats

Technical data sheet

Locomotor activity can be assessed using the rotarod apparatus. After a training phase, on testing day, rats are placed on a rotating wheel at 12 rpm and the holding time is recorded. The rotarod test assesses the effect of a drug on motor coordination and thus enables the identification of compounds possessing this liability in the form of ataxic, myorelaxant, neuroleptic or sedative effects.

Rotarod test – Rats

Technical data sheet

Numerous noninvasive techniques exist for assessing the general effects of a test substance on central nervous system (CNS) activity, as well as the gastrointestinal tract (GI tract). Among them, the Irwin test and the gastrointestinal GI transit test are routinely used to rapidly provide preliminary guidance on the common safety issues of administered drugs.

The Irwin test is used to estimate the dose range for CNS responses and the primary effects on behavior within a short period of time (several hours to the next day). The results of this test are used to identify a safe dose range, the optimal pretreatment time, and the duration of any effects to set the stage for subsequent tests of efficacy.

Gastrointestinal transit time using the charcoal meal test is commonly used to investigate the effects of drugs on gastrointestinal function.