View source for Agonists

<StructureSection load='2ace' size='350' side='right' scene='2ace/Com_view/1' caption='Torpedo californica acetylcholinesterase complex with acetylcholine, [[2ace]]' >
'''Agonists'''. A ligand that can bind to and alter the function of the receptor that triggers a physiological response is called a receptor '''agonist'''.

'''Endogenous agonists:'''
*[[Hormones]]
*[[Neurotransmitters]]
In general, receptors for small molecule neurotransmitters such as serotonin will have only one '''endogenous agonist''', but often have many different receptor subtypes (''e.g.'' 13 [[5-hydroxytryptamine receptor|different receptors for serotonin]]). On the other hand, neuropeptide receptors (e.g. [[opioid receptors]]) tend to have fewer subtypes, but may have several different endogenous agonists. This allows for a high degree of complexity in the body's signalling system, with different tissues often showing quite distinct responses to a particular ligand.

'''Exogenous agonists''' - [[Drugs]].

'''Full agonists''' bind to and activate a receptor with the maximum response that an agonist can elicit at the receptor. One example of a drug that can act as a full agonist is isoproterenol, which mimics the action of adrenaline at β-adrenoreceptors (see [[UMass Chem 423 Student Projects 2011-1#Beta-1 Adrenergic GPCR|Beta-1 Adrenergic receptor]]. Another example is morphine, which mimics the actions of endorphins at μ-opioid receptors. See 
*[[Mu Opioid Receptor Bound to a Morphinan Antagonist]]
*[[μ Opioid Receptors]]
*[[Mu Opioid Receptor]].

'''Co-agonist''' works with other co-agonists to produce the desired effect together. NMDA receptor (see [[Ionotropic Glutamate Receptors]]) activation requires the binding of both glutamate, glycine and D-serine co-agonists. Calcium can also act as a co-agonist at the [[IP3 receptor]].

'''Selective agonist''' is selective for a specific type of receptor. E.g. buspirone is a selective agonist for serotonin 5-HT1A (see [[5-hydroxytryptamine receptor]].

'''Partial agonists''' (such as buspirone, [[aripiprazole]], buprenorphine, or norclozapine) also bind and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist, even at maximal receptor occupancy. Agents like buprenorphine are used to treat opiate dependence for this reason, as they produce milder effects on the opioid receptor (see [[μ Opioid Receptors]]) with lower dependence and abuse potential. Examples of ligands activating [[PPAR-gamma|peroxisome proliferator-activated receptor gamma]] as partial agonists are honokiol and falcarindiol.

'''Inverse agonist''' is an agent that binds to the same receptor binding-site as an agonist for that receptor and inhibits the constitutive activity of the receptor. The opioid antagonists naloxone and naltrexone are also partial inverse agonists at [[μ Opioid Receptors]]. Nearly all antihistamines acting at [[Histamine H1 receptor|H1 receptors]] and H2 receptors have been shown to be inverse agonists. The beta blockers carvedilol and bucindolol have been shown to be low level inverse agonists at [[Beta-2 adrenergic receptor|beta adrenoreceptors]].

'''Superagonist''' is a term used by some to identify a compound that is capable of producing a greater response than the endogenous agonist for the target receptor. It might be argued that the endogenous agonist is simply a partial agonist in that tissue. <scene name='56/562378/3a3z/1'>The synthetic analogue (20S,23S)-epoxymethano-1alpha,25-dihydroxyvitamin D(3) (2a)</scene> acts as a 1alpha,25(OH)(2)D(3) '''superagonist''' of Vitamin D on [[Vitamin D receptor]] and exhibits both antiproliferative and prodifferentiating properties ''in vitro''.

A '''physiological agonist''' is a substance that creates the same bodily responses but does not bind to the same receptor.

'''Examples of agonists:'''  
*<scene name='56/562378/3a3z/1'>The synthetic analogue (20S,23S)-epoxymethano-1alpha,25-dihydroxyvitamin D(3) (2a)</scene> acts as a 1alpha,25(OH)(2)D(3) '''superagonist''' of Vitamin D on [[Vitamin D receptor]] and exhibits both antiproliferative and prodifferentiating properties ''in vitro''.
*<scene name='50/508426/Cvcv/6'>Agonist inositol hexakisphosphate binding site</scene> in [[Transport inhibitor response 1]] ([[3c6o]]). Water molecules are shown as red spheres.
*<scene name='54/545859/Cv/3'>Structure</scene> of human [[Bile acid receptor]] ligand-binding domain (deeppink) complex with non-steroidal agonist, nuclear receptor coactivator 1 peptide (cyan) and sulfate ions (PDB entry [[3ruu]]). <ref>PMID:21890356</ref>

</StructureSection>
== References ==
<references/>