Adrian's strategy for successful drug discovery in neuropsychiatry and neurology is based on close integration of molecular, neurochemical and behavioural pharmacology.
Areas of Expertise
Therapeutic focus: Drug discovery of novel antipsychotics, antidepressants and analgesics.
Neuropharmacology of anxiolytic / anti-stress and anti-Parkinson’s disease agents.
Principal targets: Monoamine receptors and transporters, including serotonin 5‑HT1A and 5-HT2, dopamine D2, D3 and D4 and alpha2 adrenergic receptors. N-Methyl-D-Aspartate (NMDA) receptors.
Specialty areas: Pharmacology of antipsychotics that combine D2 and 5-HT1A receptor properties.
"Biased agonism" or "functional selectivity" of serotonin 5-HT1A and 5-HT2A/2B receptor ligands.
Team management: scientific and administrative responsibility for a multidisciplinary neuropharmacology department (~20 FTEs). “Dotted-line” management of a further dozen pharmacologists in other departments.
Techniques: in vitro binding, signal transduction, autoradiography. Neurochemistry of neurotransmitter release by microdialysis in rodent. Behavioural tests of psychostimulant effects, mood / stress and cognition. Translational models, micro-PET, effects of antipsychotics in dog and non-human primate.
Examples of drugs characterised:
Milnacipran (Ixel ®, Savella ®): antidepressant and anti-fibromyalgia agent that inhibits serotonin and noradrenaline reuptake. Characterisation of analgesic activity and in models of chronic stress.
Piribedil (Trivastal ®): antiparkinson agent. Demonstration that it possesses alpha2 adrenoceptor antagonist properties in addition to dopamine D2 receptor partial agonism.
Agomelatine (Valdoxan ®): antidepressant agent and melatonin agonist. Demonstration of its antagonist properties at serotonin 5-HT2C and 5-HT2B receptors.
Befiradol (=F13640; Phase II): anti-neuropathic pain agent with high efficacy and selectivity at serotonin 5-HT1A receptors. Characterisation of its activity at 5-HT1A receptor subpopulations.
S33138 (Ph.II, discontinued): potential antipsychotic. Characterisation of its preferential dopamine D3 versus D2 receptor affinity and antagonism at these sites.
F15599 (Ph.I, discontinued): potential antidepressant and selective serotonin 5-HT1A receptor agonist. Demonstration of its preferential activation of 5-HT1A receptors in frontal cortex.
F15063 (Pre-clinical, discontinued): potential antipsychotic with D2 / D3 antagonism, 5-HT1A and D4 partial agonism. Active in models of positive, negative and cognitive symptoms of schizophrenia.