Transmembrane domains neuropeptide receptors

While the agonist binding domain is thought to be within the transmembrane domains for the monoamine and nucleotide receptors, neuropeptides are thought to bind close to the membrane surface on the extracellular domains of the receptor. It is still not clear whether non-peptide antagonists bind at the same or a different site on the receptor. 

Most neuropeptide receptors are seven-transmembrane-domain, G-protein-coupled receptors 326 Neuropeptide receptors are not confined to synaptic regions 327 Expressions of peptide receptors and the corresponding peptides are not well matched 327... 

A large cyclic neuropeptide can indeed penetrate the core transmembrane domain of its receptor. 

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