melior melior discovery melior pharmaceuticals preclinical services pre-clinical services in vivo pharmacology in vivo efficacy efficacy models pharmacokinetics indications discovery specialized animal models bioanalytical services theratrace exton pennsylvania cro contract research drug discovery drug development metabolic disease alzheimer’s alzheimers diabetes reprofiling
Melior Discovery
home
Therapeutic Areas
Safety Assessment
 


theraTRACE

Melior Pharmaceuticals

 

melior melior melior discovery melior pharmaceuticals preclinical services pre-clinical services in vivo pharmacology in vivo efficacy efficacy models pharmacokinetics indications discovery specialized animal models bioanalytical services theratrace exton pennsylvania cro contract research drug discovery drug development metabolic disease alzheimer’s alzheimers diabetes reprofiling

Melior Discovery general safety assessment

Irwin Observational Battery
The Irwin test is an observational screening test that is a battery of tests used to assess a mouse or rat's neurobiological and physiological state.  Parameters that are evaluated include autonomic and sensorimotor functions, convulsive behavior, and other activities produced by a drug after administration.  When conducted by an experienced tester the Irwin test can provide insight into a drug's activity including potential molecular targets, therapeutic benefits and deleterious side-effects. 

The modified Irwin test describe is used to identify subtle neurological pertubations produced by a drug and used to control for other behavioral and locomotor assays described in the Melior Discovery platform. Although a behavioral test of sorts, it is not directed towards a specific indication.  The Irwin test is principally used by Melior to provide a context for other assays.  This assay system will also be used during the pharmacokinetic and maximal tolerated dose preliminary studies to establish dose-response ranges for subsequent efficacy studies.  In this study, we assessed Diazepam, a centrally acting anxiolytic with some sedative activities in three different strains of mice: male CD1, male DBA1 and female SJL/J mice. 

 

Mice were assessed for the features described betwlow by two observers blinded to the treatment, 30 minutes after vehicle or Diazepam administration.  Each parameter was scored on a 0 to 5 scale, with 0 representing the response in a normal animal and 5 representing a maximally impaired animal. 

 

Figure 1: In Cage Observations

                             Irwin Testing In Cage Observation

In cage observations and modified Irwin battery scores.  Animals were dosed with vehicle or Diazepam 30 minutes prior to assessment.  In cage observations include general apperance, hyperactivity, hypoactivity, sedation or seizure activity. Hypoactivity was signifcantly increased in Diazepam treated CD1 (A) and DBA1 (B) mice while sedation was significantly increased in Diazepam treated SJL/J mice.  Data are mean ±  SEM; **p<0.01, ***p<0.001 compared to vehicle.

 

Figure 2: Suspended Tests

                       Irwin Testing Suspended Tests

 

Suspended tests and modified Irwin battery scores.  Animals were dosed with vehicle or Diazepam 30 minutes prior to assessment. Suspended tests include suspended body placement, crossed extensor reflex, forelimb hindlimb placing, grasp reflex and bar holding.  Forelimb handlimb placing and grasp reflex scores (A) were significantly increased in Diazepam treated CD1 mice and suspended body placement was signficantly increaed in Diazepam treated SJL/J mice (C).  There were no signficant changes in DBA1 mice (B).  Data are mean ±  SEM; **p<0.01, ****p<0.0001 compared to vehicle.

 

Figure 3: Autonomic Responses

                     Irwin Testing Autonomic Response

Autonomic responses and modified Irwin battery scores.  Animals were dosed with vehicle or Diazepam 30 minutes prior to assessment. Autonomic response tests include righting reflex, tail pinch, auditory startle and defecation.  In Diazepam treated mice, auditory startle and defecation were significantly increased in CD1 mice (A) and DBA1 mice (B).  There were no significant differences in SJL/J treated mice, however an increased trend is present (C).  Data are mean ±  SEM; **p<0.01, ****p<0.0001 compared to vehicle.

 

Figure 4: Fecal Pellets

                               Irwin Test Fecal Pellet

 

Fecal pellet production and modified Irwin battery scores.  Animals were dosed with vehicle or Diazepam 30 minutes prior to assessment. There were no significant differences in fecal pellet production between all three groups (A-C). Data are mean ±  SEM.

 

If you are interested in learning more about the Irwin general safety assessment for mice or rats, please contact models@meliordiscovery.comto start the conversation.