DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

Table 14–8
Examples of Neuropeptides
Calcitonin Family
Calcitonin
Calcitonin gene-related peptide (CGRP)
Hypothalamic Hormones
Oxytocin
Vasopressin
Hypothalamic Releasing and Inhibitory Hormones
Corticotropin-releasing factor (CRF or CRH)
Gonadotropin-releasing hormone (GnRH)
Growth hormone releasing hormone (GHRH)
Somatostatin (SST)
Thyrotropin releasing hormone (TRH)
Neuropeptide Y Family
Neuropeptide Y (NPY)
Neuropeptide YY (PYY)
Pancreatic polypeptide (PP)
Opioid Peptides
β-endorphin (also pituitary hormone)
Dynorphin peptides
Leu-enkephalin
Met-enkephalin
Pituitaty Hormones
Adrenocorticotropic hormone (ACTH)
α-Melanocyte-stimulating hormone (α-MSH)
Growth hormone (GH)
Follicle-stimulating hormone (FSH)
β-lipotropin (β-LPH)
Luteinizing hormone (LH)
Tachykinins
Neurokinin A (substance A)
Neurokinin B
Neuropeptide K
Substance P
VIP-Glucagon Family
Glucagon
Glucagon-like peptide (GLP-1)
Pituitary adenylyl cyclase—activating peptide (PACAP)
Vasoactive intestinal polypeptide (VIP)
Some Other Peptides
Agouti-related peptide (ARP)
Bombesin
Bradykinin (BK)
Cholecystokinin (CCK; multiple forms)
Cocaine- and amphetamine-regulated transcript (CART)
Galanin
Ghrelin
Melanin-concentrating hormone (MCH)
Neurotensin
Nerve growth factor (NGF)
Orexins (or Hypocretins)
Orphanin GQ (or Nociceptin) (also grouped with opioids)
Modified with permission from Nestler, E.J., Hyman, S.E., and Malenka, R.C. Molecular Neuropharmacology. McGraw-Hill, New York, 2009,
page 184, Table 7–1.
cortical cells responds to ACTH, while that on melanocytes responds
to α- MSH. Further evidence for complexity comes from the realization
that agonists at subtypes of melanocortin receptors are associated
with a variety of biological effects including skin darkening
(MCR1), decreased appetite (MCR3 and/or MCR4), and sexual
arousal (MCR4).
Although most peptide receptors are GPCRs, exceptions do
exist. The amiloride-sensitive FMRF amide (phe- met- arg- pheamide)
receptor is a peptide-gated ion channel. The large number of
neuropeptides and peptide receptors has lead to increased interest in
identifying therapeutic agents. Examples include experimental substance
P antagonists as antidepressants or to treat anxiety, and antagonists
of CRH for stress related disorders.
Comparison with Other Transmitters. Peptides differ in several
important respects from the monoamine and amino acid transmitters.
Peptide synthesis takes place in the rough endoplasmic reticulum.
The propeptide is cleaved (processed) to the secreted form as
secretory vesicles are transported from the perinuclear cytoplasm
to the nerve terminal. Active mechanisms for the local synthesis
of peptides have not been described; thus, peptidergic nerve
terminals depend on distant sites of synthesis. As for structureactivity
relationships for peptide transmitters, linear chains of
amino acids can assume many conformations at their receptors,
making it difficult to define the sequences and their steric relationships
that are critical for activity. Until recently, it was difficult to
develop non- peptidic synthetic agonists or antagonists that interact
with specific peptide receptors. Such agents now are being developed
for many neuropeptides (Hökfelt et al., 2003). Natural products
have not been good sources of drugs that affect peptidergic
transmission. Only one plant alkaloid, morphine, has been found to
act selectively at peptidergic synapses. Fortunately for pharmacologists,
morphine was discovered before the endorphins, or rigid