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In general, receptors for small moleculeneurotransmitters such as serotonin will have only one endogenous agonist, but often have many different receptor subtypes (e.g. 13 different receptors for serotonin). On the other hand, neuropeptide 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. Some endogenous antagonists and inverse agonists are also known (e.g., kynurenic acid at the NMDA receptor), but these are much less common.
References
Goodman and Gilman's Manual of Pharmacology and Therapeutics. (11th edition, 2008). p14. ISBN0-07-144343-6