Table 1. Approved drugs targeting neuropeptide receptors and neuropeptides used as biomarkers or diagnostic tools.a .
| DRUGS | ||
|---|---|---|
| Receptor | Receptor subtypes | Drug and indication |
| Angiotensin (AT) receptor | AT1 and AT2 receptors |
Small molecules:
Valsartan, Losartan, Irbesartan, Olmesartan, Eprosartan, Telmisartan, AT1 antagonists for hypertension; Candesartan, AT1 antagonist for chronic heart failure. |
| Bradykinin receptors | B1, B2 receptors |
Peptide:
Icatibant, selective B2 receptor antagonist, for hereditary angioedema. |
| Calcitonin (CT) receptor | CT receptor |
Peptides:
Synthetic salmon calcitonin or synthetic human calcitonin for the treatment of hypercalcemia (postmenopausal osteoporosis, Paget’s disease of bone, Sudeck’s atrophy, and malignancy-associated hypercalcemia)[174]. |
| Endothelin (ET) receptors | ETA and ETB receptors |
Small molecules:
Bosentan and Macitentan, dual receptor antagonists; Ambrisentan, a selective ETA receptor antagonist; All used for the treatment of pulmonary hypertension [175]. |
| Glucagon receptors | Glucagon receptor, GLP-1 receptor b, GLP-2 receptor |
Peptides:
Recombinant glucagon, for severe hypoglycaemia; Exenatide, liraglutide, albiglutide, lixisenatide, dulaglutide, semaglutide, GLP-1 receptor agonists, used for diabetes treatment; Teduglutide, human GLP-2 analogue, used for short bowel syndrome, malabsorption. |
| Gonadotropin-releasing hormone (GnRH) receptor | GnRH receptor |
Peptides:
Nafarelin, GnRH receptor agonist used for treatment of central precocious puberty and endometriosis; Cetrorelix, GnRH receptor antagonist used to inhibit premature luteinizing hormone surges in controlled ovarian stimulation; Elagolix, GnRH receptor antagonist, used for management of moderate to severe pain associated with endometriosis; Degarelix, GnRH receptor antagonist, used for management of advanced prostate cancer; Leuprolide, GnRH agonist, used to treat prostate cancer, endometriosis, uterine fibroids and premature puberty. |
| Growth hormone receptor | Growth hormone receptor |
Peptide / protein:
Somatotropin, recombinant human growth hormone, used for growth hormone deficiency, Turner syndrome, Noonan syndrome, Prader-Willi syndrome, short stature homeobox-containing gene deficiency, chronic renal insufficiency, idiopathic short stature and children small for gestational age; Pegvisomant, growth hormone receptor antagonist, used for acromegaly. |
| Growth hormone releasing hormone (GHRH) receptor | GHRH receptor |
Peptides:
Sermorelin, GHRH1–29 peptide fragment, for treatment of growth failure in children; Tesamorelin, GHRH1–44 peptide fragment, for lipodystrophy in HIV patients. |
| Insulin receptor | Insulin receptor, IGF-1 c receptor |
Peptides:
Human insulin, used for glycaemic control in patients with diabetes mellitus; Mecasermin, recombinant human IGF-1, approved for growth failure in children with primary insulin-like growth factor-1 deficiency or growth hormone gene deletion. |
| Leptin receptor | Leptin receptor |
Peptide:
Metreleptin, a leptin analogue used for diabetes and/or hypertriglyceridemia. |
| Melanocortin (MC) receptors | MC1-5 receptors |
Peptide:
Bremelanotide, MC1, MC3-5 agonist, used for premenopausal women with hypoactive sexual desire disorder. |
| Natriuretic peptide receptors (NPR) | NPR-A, -B, and -C receptors |
Small molecules:
Nitroprusside, Nitroglycerin, Isosorbide dinitrate, Erythrityl tetranitrate, and Amyl nitrite, act as nitric oxide source, vasodilators used for chest pain and high blood pressure. Peptide: Nesiritide, recombinant human BNP d for congestive heart failure. |
| Opioid receptors | µ-, δ-, κ-opioid receptors |
Small molecules:
Butorphanol, Tramadol, Sufentanil, Alfentanil, Hydrocodone, Fentanyl, Dextropropoxyphene, Morphine, Codeine, Hydromorphone, Meperidine, µ-, δ-, and/or κ-opioid receptor agonists for pain management, anaesthetic, analgesia; Naltrexone, Nalbuphine, Buprenorphine, Dezocine, Pentazocine, Naloxone, Levallorphan, µ-, δ-, and/or κ-opioid receptor antagonists for pain and/or addiction management, treatment of narcotic depression. |
| Orexin (OX) receptors | OX1, OX2 receptors |
Small molecule:
Suvorexant, OX1R and OX2R antagonist used for insomnia. |
| Parathyroid hormone (PTH) type 1 receptor | PTH type 1 receptor |
Peptides:
Teriparatide, recombinant human PTH used in treatment of osteoporosis; Abaloparatide, PTH-related protein analogue, used for post-menopausal women with osteoporosis. |
| Somatostatin (SST) receptors | SST1-5 receptors |
Peptides:
Octreotide, lanreotide, SST2 / SST5 receptor agonists used for acromegaly and to reduce cancer chemotherapy side effects; Pasireotide, pan agonist used for Cushing’s Disease; |
| Tachykinin receptors | NK1, NK2, NK3, Neuromedin-K receptors |
Small molecules:
Fosaprepitant, Aprepitant, Netupitant, Rolapitant, NK1 antagonist used for chemotherapy-induced emesis. |
| Oxytocin (OT) and vasopressin receptors | OT, V1a, V1b, V2 receptors |
Peptides:
Atosiban, OTR antagonist used as labour suppressant and IVF treatment; Pitocin and Carbetocin, OTR agonists used for labour induction, post-partum bleeding, and haemorrhage; Desmopressin, V2R agonist for diabetes insipidus and nocturnal enuresis; Terlipressin, V2R agonist used to stop bleeding in the oesophagus. Small molecules: Conivaptan, V1aR and V2R antagonist used for hyponatremia; Tolvaptan, V2R antagonist used for hyponatremia. |
|
| ||
| BIOMARKERS OR DIAGNOSTIC TOOLS | ||
| Neuropeptide | Receptor | Compound and application |
|
| ||
| ATCH | MC2 receptor | Diagnostic agent used to screen for adrenocortical insufficiency. |
| BNP | n.a.e | Diagnostic marker for heart failure [176]. |
| Chromogranin A | n.a. | An indicator for pancreas and prostate cancer in carcinoid syndrome [177]. |
| Corticotropin-releasing hormone (CRH) | CRH receptor 1 | Corticorelin, synthetic human CRH, is used to test the HPA axis and ATCH secretion. |
| Gastrin | n.a. | Diagnostic marker for gastrin-secreting tumours, atrophic gastritis, gastric ulcers, and pernicious anaemia [178]. |
| Ghrelin | Ghrelin receptor | Ghrelin mimetic Macimorelin is used to diagnose adult GH deficiency. |
| GnRH | GnRH receptor | Gonadorelin, synthetic GnRH, is used to evaluate anterior pituitary performance. |
| Insulin | Insulin receptor | Biomarker for diabetes (complementary); used for identification of insulinomas; insulin-induced hypoglycaemia test used to diagnose suspected ACTH or growth hormone deficiency [179]. |
| Pancreatic polypeptide | n.a. | Diagnostic test of vagal nerve function [180]. |
| Procalcitonin Prolactin | n.a. n.a. | A biomarker of infection and sepsis [181, 182]. Diagnostic marker in sex hormone check-up; epilepsy type diagnosis [21]. |
| Thyrotropin-releasing hormone (TRH) | TRH receptor | Protirelin, a TRH analogue, is used to test anterior pituitary gland function to aid thyroid disorder diagnosis [183]. |
| Somatostatin | SST1–5 receptors | Various radiolabelled somatostatin analogues used for cancer treatment (e.g. Edotreotide gallium Ga-68 and Lutetium Lu 177 dotatate). |
a
Information from DrugBank database (www.drugbank.ca) [184] where an ‘approved’ drug has been approved in at least one jurisdiction, anywhere;
b
GLP, Glucagon-like peptide;
c
IGF, insulin-like growth factor;
d
BNP, B-type natriuretic peptide;
e
n.a. Not applicable.