Intranasal antipsychotic administration: a viable route of administration to avoid debilitating peripherally-induced side-effects  — The Association Specialists
  1. Schedule
  2. Poster Presentations
  3. Intranasal antipsychotic administration: a viable route of administration to avoid debilitating peripherally-induced side-effects 

Intranasal antipsychotic administration: a viable route of administration to avoid debilitating peripherally-induced side-effects  (21360)

Darryl W Eyles 1 2 , Suzy Alexander 2 , Emma Hilsley , Harendra Parekh 3 , Preeti Pandey 3 , Masood Ali 3
  1. Queensland Brain Institute, University of Queensland, St Lucia, QLD, Australia
  2. Queensland Centre for mental health research, Brisbane, Qld, Australia
  3. PACE, University of Queensland, Brisbane, Qld

Clozapine is the most effective antipsychotic drug for Treatment Resistant Schizophrenia, yet it has severe debilitating metabolic and potentially lethal immune-related side effects. Most of these side effects are peripherally mediated. We are exploring whether administering clozapine via the intranasal (IN) route, which largely avoids the periphery, can still act as an antipsychotic while hopefully avoiding such side-effects.

Suppression of the Conditioned Avoidance Reaction (CAR) in experimental animals is a unique feature of all antipsychotic agents. The aim of this study was to determine if IN clozapine suspended in a patented Sol-Gel nano-emulsion could also suppress CAR.

Male Sprague-Dawley rats were trained to associate the presentation of a tone (Conditioned Stimulus, CS), with a mild footshock. Animals learn and on presentation of the CS move to the alternate chamber to avoid the foot shock. Antipsychotics all uniquely interfere with this learned behaviour largely via their actions at post-synaptic D2 receptors.

INCloz (0.7mg/kg) produced a similar profile of CAR suppression over time as 20mg/kg oral Cloz. These doses were selected based on their ability to suppress CAR without inducing unwanted cataleptic / tranquilizing effects which were observed at higher doses (INCloz 1.16mg/kg, oral Cloz 30mg/kg). Brain and blood collected 30 minutes post INCloz administration were analysed using HPLC and show clozapine levels 5.5 times higher in the brain vs the blood.

We show intranasal administration can produce an antipsychotic behavioural effect at a fraction (3.5%) of the dose used orally. This offers great promise for planned future clinical trials in patients.