Glossary category

Pharmacology

Terms describing how a compound acts and how the body handles it.

Terms

27 documents

Table 1. Terms in the pharmacology category.

Term	Definition
AcylationLipidation	Attachment of a fatty-acid chain to a peptide, most often to mediate reversible albumin binding and thereby extend half-life. The structural feature underlying weekly dosing in this class.
Agonist	A ligand that binds a receptor and produces a response. Full agonists produce the maximal response the system can give; partial agonists produce less at full occupancy.
Amylin	A pancreatic hormone co-secreted with insulin that slows gastric emptying and promotes satiation through the area postrema. Amylin analogues act on a mechanism largely separate from that of the incretins.
Amylin analogue	A compound activating amylin and calcitonin receptors, producing meal-related satiation. Combined with an incretin agonist in at least one fixed-combination product in this set.
Antagonist	A ligand that binds a receptor without producing a response and prevents an agonist from doing so.
Area postrema	A circumventricular structure lacking a complete blood–brain barrier, accessible to circulating peptides and central to both the satiety and the nausea effects of this compound class.
Biased agonismFunctional selectivity	Preferential activation of one signalling pathway over another from the same receptor. Proposed as a means of separating a desired effect from receptor internalisation and desensitisation.
Bioavailability	The fraction of an administered dose reaching the systemic circulation unchanged. Low and variable for orally administered peptides, which is the constraint every oral peptide presentation exists to address.
Clearance	The volume of plasma cleared of a compound per unit time. Together with volume of distribution it determines half-life.
Desensitisation	Reduction in receptor responsiveness following sustained stimulation, often through receptor internalisation. The pharmacological reason that non-pulsatile administration of a hypothalamic releasing hormone suppresses rather than stimulates its axis.
Dose–response	The relationship between dose and the magnitude of effect. A monotonic relationship supports causal attribution; a non-monotonic one is reported by the Institute as observed rather than smoothed.
DPP-4Dipeptidyl peptidase-4	Dipeptidyl peptidase-4, the protease that cleaves native glucagon-like peptide-1 within minutes. Every long-acting analogue in this set is protected against it structurally.
Dual agonistCo-agonist	A single molecule engineered to activate two receptors. In this document set the combinations of interest are GIP with GLP-1, and glucagon with GLP-1, which produce different profiles.
Enzymatic degradationProteolysis	Breakdown of a peptide by proteases, principally dipeptidyl peptidase-4 for incretins. Resistance is engineered by substitution at the cleavage site.
Gastric emptying	The rate at which stomach contents pass into the duodenum. Delayed by GLP-1 receptor agonism, with partial attenuation on continued dosing, and relevant to both postprandial glucose and to procedural sedation.
GIPGlucose-dependent insulinotropic polypeptide	Glucose-dependent insulinotropic polypeptide, the second human incretin. Its contribution to the effects of dual agonists is substantially supported and not fully established.
GLP-1 receptor agonistGlucagon-like peptide-1 receptor agonist	A compound activating the glucagon-like peptide-1 receptor, a class B G protein-coupled receptor signalling principally through Gαs. Effects include glucose-dependent insulin secretion, glucagon suppression, delayed gastric emptying and reduced energy intake.
Half-lifeTerminal half-life · t½	The time for a plasma concentration to fall by half during the terminal elimination phase. Determines dosing interval, time to steady state and the time required for washout.
Incretin	A gut-derived hormone that potentiates insulin secretion in response to nutrient intake. The two principal human incretins are glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide.
Partial agonist	A ligand producing a submaximal response at full receptor occupancy. May behave as an antagonist in the presence of a full agonist.
Permeation enhancer	An excipient that increases absorption across a mucosal surface. In the oral peptide presentation in this document set it transiently raises local pH and increases membrane permeability, and imposes an administration window that constrains adherence.
Plasma protein binding	The fraction of a compound bound to circulating protein and therefore not immediately available to distribute or be eliminated. Reversible albumin binding is the mechanism by which several compounds in this set achieve a weekly dosing interval.
Steady state	The condition in which the amount of a compound entering the body equals the amount leaving it. Reached after approximately four to five half-lives of repeated dosing.
Tachyphylaxis	Rapid attenuation of response with repeated administration. Documented for several growth-hormone secretagogues and material to any claim about sustained effect.
TmaxTime to maximum concentration	The time from administration to the maximum observed plasma concentration. For a subcutaneously administered acylated peptide this is measured in days rather than hours.
Triple agonist	A single molecule activating three receptors, in this set GIP, GLP-1 and glucagon. The glucagon component contributes an energy-expenditure effect and a hepatic effect that the other two do not.
Volume of distributionVd	The apparent volume into which a compound distributes, computed from dose and plasma concentration. A small value indicates confinement to the circulation, as expected for an albumin-bound peptide.