Receptor Pharmacology
for Neurology and Neuroscience

At Gifford Bioscience, we have extensive experience working with novel therapeutics targeting Alzheimer’s, Parkinson’s and Huntington’s disease as well as psychiatric conditions. We characterise receptor pharmacology from membrane preparations through to native, endogenous brain tissue, generating the binding and functional data that drives CNS drug discovery

Case Study

Muscarinic acetylcholine receptors

Muscarinic receptors have become one of the most active targets in psychiatry following the approval of xanomeline-trospium (KarXT) for schizophrenia, the first non-dopaminergic antipsychotic in a generation. With M₁ agonism pursued for cognition and M₄ agonism for the modulation of striatal dopamine, programmes need binding and functional data generated where these receptors sit at native density and couple to their physiological G-proteins.

We profiled muscarinic pharmacology in native brain tissue across both binding and function. Competition binding with the antagonist radioligand [³H]QNB quantifies compound affinity, while our Gα_q-specific [³⁵S]GTPγS SPA-bead assay confirms agonist-driven receptor activation, together giving a complete affinity-plus-efficacy readout at the native receptor.

Muscarinic receptor pharmacology in native tissue. (A) Scopolamine displaces [³H]QNB from mouse whole-brain membranes (IC₅₀ 134.1 nM; Log IC₅₀ −8.873). (B) Oxotremorine-M stimulates Gα_q-specific [³⁵S]GTPγS binding in rat striatum (Log EC₅₀ −6.181).

Case Study

Serotonin (5-HT) receptors

The serotonin system is at the centre of the psychedelic renaissance in psychiatry. 5-HT_2A is the principal target of psilocybin, DOI and related compounds, several of which are now in late-stage trials for treatment-resistant depression and PTSD. Because the 5-HT family spans fourteen subtypes with overlapping pharmacology, both selectivity and functional efficacy must be measured with care, a compound’s affinity tells only part of the story.

We characterised 5-HT_2A pharmacology in native rat brain across binding and function. Competition binding with [³H]ketanserin establishes affinity and regional consistency, while our Gα_q-specific [³⁵S]GTPγS assay ranks three psychedelic agonists by functional potency, directly supporting the structure-activity work behind this emerging therapeutic class.

5-HT_2A receptor pharmacology in native tissue. (A) Ketanserin displaces [³H]ketanserin at 5-HT_2A in rat cortex (Log IC₅₀ −7.801) and striatum (−7.581). (B) Gα_q activation by 25I-NBOMe (Log EC₅₀ −7.449), DOI (−7.079) and psilocin (−6.079) in rat striatum.

Case Study

We applied our expertise in receptor pharmacology to a study investigating the effect of methylone as a rapid-acting neuroplastogen with greater specificity than MDMA. This finding supports methylone’s potential use in the treatment of PTSD and other neuropsychiatric disorders.

Read the publication here.

Determination of drug-evoked release of radiolabeled (A) 5HT, (B) NE or (C) DA by methylone or MDMA from rat brain synaptosomes. Data shown are means ± SEM. N = 3 per group.

Radioligand Binding Assays determine receptor-ligand binding affinity (K_d, IC₅₀, K_i), density of binding sites (B_max) and binding kinetics (k_on/k_off) in cell lines or to native receptors in human or animal tissue.

Autoradiography and Receptor Occupancy determine target engagement of test drugs to receptors in the animal. These assays visualise and quantify receptor-ligand binding interactions in tissue from naive and drug-treated animals.

SPR assesses binding affinity, inhibition (K_d, IC₅₀, K_i) and kinetics of therapeutics at the target of interest (k_on/k_off), or investigate protein-protein interactions.

Functional Cell Signalling Assays are radiometric and fluorescence-based assays to profile the physiological effects of compounds by measuring GPCR activation (GTPγS) and downstream signalling (cAMP, Ca2+, phospho-ERK assay) as a result of agonist, antagonist, or inverse agonist treatment (EC₅₀, E_max, IC₅₀).

Radioimmunoassay and ELISAs monitor receptor expression, detect disease markers using radiolabelled antibodies and determine concentration of targets upon drug treatment.

Uptake and Release Assays measure the transport of radiolabeled compounds or neurotransmitters into cells or synaptosomes; the release of the radiolabeled compounds or neurotransmitters and inhibition by test compounds.

What our Partners say about Gifford Bioscience

From initial inquiry to project debrief, it’s our collaborative style that sets us apart. Our 100% PhD level scientists use their deep expertise to help you solve even the most complex of scientific challenges. Visit our testimonials page to see how our Neurology CRO services have helped our partners achieve quality outcomes in the development of heir novel therapeutics.