Octreotide
|
|
| Systematic (IUPAC) name |
(4R,7S,10S,13R,16S,19R)-10-(4-aminobutyl)-19-
[[(2R)-2-amino-3-phenyl-propanoyl]amino]-16-
benzyl-N-[(2R,3R)-1,3-dihydroxybutan-2-yl]-7-
(1-hydroxyethyl)-13-(1H-indol-3-ylmethyl)-6,9,12,
15,18-pentaoxo-1,2-dithia-5,8,11,14,17-
pentazacycloicosane-4-carboxamide |
| Clinical data |
| Trade names |
Sandostatin |
| AHFS/Drugs.com |
monograph |
|
Pregnancy
category
|
|
|
Legal status
|
- AU: Prescription Only (S4)
- CA: ℞-only
- UK: POM
- US: ℞-only
|
|
Routes of
administration
|
Subcutaneous, intramuscular, intravenous |
| Pharmacokinetic data |
| Bioavailability |
60% (IM), 100% (SC) |
| Protein binding |
40–65% |
| Metabolism |
Hepatic |
| Half-life |
1.7–1.9 hours |
| Excretion |
Urine (32%) |
| Identifiers |
|
CAS Registry Number
|
83150-76-9 Y
79517-01-4 (acetate)
135467-16-2 (pamoate) |
|
ATC code
|
H01CB02 |
| PubChem |
CID 383414 |
| DrugBank |
DB00104 Y |
| ChemSpider |
10482007 Y |
| UNII |
RWM8CCW8GP Y |
| KEGG |
D00442 N |
| ChEMBL |
CHEMBL1680 N |
| Chemical data |
| Formula |
C49H66N10O10S2 |
|
Molecular mass
|
1019.24 g/mol |
SMILES
- C[C@@H](O)[C@@H](CO)NC(=O)[C@@H]5CSSC[C@H](NC(=O)[C@H](N)Cc1ccccc1)C(=O)N[C@@H](Cc2ccccc2)C(=O)N[C@H](Cc4cnc3ccccc34)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)O)C(=O)N5
|
InChI
-
InChI=1S/C49H66N10O10S2/c1-28(61)39(25-60)56-48(68)41-27-71-70-26-40(57-43(63)34(51)21-30-13-5-3-6-14-30)47(67)54-37(22-31-15-7-4-8-16-31)45(65)55-38(23-32-24-52-35-18-10-9-17-33(32)35)46(66)53-36(19-11-12-20-50)44(64)59-42(29(2)62)49(69)58-41/h3-10,13-18,24,28-29,34,36-42,52,60-62H,11-12,19-23,25-27,50-51H2,1-2H3,(H,53,66)(H,54,67)(H,55,65)(H,56,68)(H,57,63)(H,58,69)(H,59,64)/t28-,29?,34-,36+,37+,38-,39-,40+,41+,42+/m1/s1 Y
Key:DEQANNDTNATYII-RRCPSWKPSA-N Y
|
| N (what is this?) (verify) |
Octreotide (brand name Sandostatin,[1] Novartis Pharmaceuticals) is an octapeptide that mimics natural somatostatin pharmacologically, though it is a more potent inhibitor of growth hormone, glucagon, and insulin than the natural hormone. It was first synthesized in 1979 by the chemist Wilfried Bauer.
Contents
- 1 Medical uses
- 1.1 Tumors
- 1.2 Bleeding esophageal varices
- 1.3 Radiolabelling
- 2 Contraindications
- 3 Adverse effects
- 4 Interactions
- 5 Pharmacological effects
- 6 Pharmacokinetics
- 7 Research
- 8 See also
- 9 References
Medical uses
Tumors
Octreotide is used for the treatment of growth hormone producing tumors (acromegaly and gigantism), pituitary tumors that secrete thyroid stimulating hormone (thyrotropinoma), diarrhea and flushing episodes associated with carcinoid syndrome, and diarrhea in people with vasoactive intestinal peptide-secreting tumors (VIPomas).
Bleeding esophageal varices
Octreotide is often given as an infusion for management of acute haemorrhage from esophageal varices in liver cirrhosis on the basis that it reduces portal venous pressure, though current evidence suggests that this effect is transient and does not improve survival.[2]
Radiolabelling
Further information: Octreotide scan
Octreotide is used in nuclear medicine imaging by labelling with indium-111 (Octreoscan) to noninvasively image neuroendocrine and other tumours expressing somatostatin receptors.[3] More recently, it has been radiolabelled with carbon-11[4] as well as gallium-68, enabling imaging with positron emission tomography (PET), which provides higher resolution and sensitivity.
Octreotide can also be labelled with a variety of radionuclides, such as yttrium-90 or lutetium-177, to enable peptide receptor radionuclide therapy (PRRT) for the treatment of unresectable neuroendocrine tumours.
Contraindications
Octreotide has not been adequately studied for the treatment of children, pregnant and lactating women. The drug is given to these groups of patients only if a risk-benefit analysis is positive.[5][6]
Adverse effects
The most frequent adverse effects (more than 10% of patients) are headache, hypothyroidism, cardiac conduction changes, gastrointestinal reactions (including cramps, nausea/vomiting and diarrhoea or constipation), gallstones, reduction of insulin release, hyperglycemia[7] or hypoglycemia, and (usually transient) injection site reactions. Slow heart rate, skin reactions such as pruritus, hyperbilirubinemia, hypothyroidism, dizziness and dyspnoea are also fairly common (more than 1%). Rare side effects include acute anaphylactic reactions, pancreatitis and hepatitis.[5][6] One study reported a possible association with rheumatoid arthritis.[8]
Some studies reported alopecia in patients who were treated by octreotide.[9] Rats which were treated by octreotide experienced erectile dysfunction in a 1998 study.[10]
A prolonged QT interval has been observed in patients, but it is uncertain whether this is a reaction to the drug or part of the patients' illnesses.[5]
| Identifiers |
| OPM superfamily |
167 |
| OPM protein |
1soc |
Interactions
Octreotide can reduce the intestinal resorption of ciclosporin, possibly making it necessary to increase the dose.[11] Patients with diabetes mellitus might need less insulin or oral antidiabetics when treated with octreotide. The bioavailability of bromocriptine is increased;[6] besides being an antiparkinsonian, bromocriptine is also used for the treatment of acromegaly.
Pharmacological effects
Since octreotide resembles somatostatin in physiological activities, it can:
- inhibit secretion of many hormones, such as gastrin, cholecystokinin, glucagon, growth hormone, insulin, secretin, pancreatic polypeptide, TSH, and vasoactive intestinal peptide,
- reduce secretion of fluids by the intestine and pancreas,
- reduce gastrointestinal motility and inhibit contraction of the gallbladder,
- inhibit the action of certain hormones from the anterior pituitary,
- cause vasoconstriction in the blood vessels, and
- reduce portal vessel pressures in bleeding varices.
It has also been shown to produce analgesic effects, most probably acting as a partial agonist at the mu opioid receptor.[12][13]
Pharmacokinetics
Octreotide is absorbed quickly and completely after subcutaneous application. Maximal plasma concentration is reached after 30 minutes. The elimination half-life is 100 minutes (1.7 hours) on average when applied subcutaneously; after intravenous injection, the substance is eliminated in two phases with half-lives of 10 and 90 minutes, respectively.[5][6]
Research
Octreotide has also been used off-label for the treatment of severe, refractory diarrhea from other causes. It is used in toxicology for the treatment of prolonged recurrent hypoglycemia after sulfonylurea and possibly meglitinides overdose. It has also been used with varying degrees of success in infants with nesidioblastosis to help decrease insulin hypersecretion. Several clinical trials also proves the effect of octreotide as acute treatment (abortive agent) in cluster headache, where it shows that administration of subcutaneous octreotide is effective when compared with placebo. [14]
Octreotide has been used experimentally to treat obesity, particularly obesity caused by lesions in the hunger and satiety centers of the hypothalamus, a region of the brain central to the regulation of food intake and energy expenditure.[15] The circuit begins with an area of the hypothalamus, the arcuate nucleus, that has outputs to the lateral hypothalamus (LH) and ventromedial hypothalamus (VMH), the brain's feeding and satiety centers, respectively.[16][17] The VMH is sometimes injured by ongoing treatment for acute lymphoblastic leukemia (ALL) or surgery or radiation to treat posterior cranial fossa tumors.[15] With the VMH disabled and no longer responding to peripheral energy balance signals, "Efferent sympathetic activity drops, resulting in malaise and reduced energy expenditure, and vagal activity increases, resulting in increased insulin secretion and adipogenesis."[18] "VMH dysfunction promotes excessive caloric intake and decreased caloric expenditure, leading to continuous and unrelenting weight gain. Attempts at caloric restriction or pharmacotherapy with adrenergic or serotonergic agents have previously met with little or only brief success in treating this syndrome."[15] In this context, octreotide suppresses the excessive release of insulin and may increase its action, thereby inhibiting excessive adipose storage. In a small clinical trial in eighteen pediatric patients with intractable weight gain following therapy for ALL or brain tumors and other evidence of hypothalamic dysfunction, octreotide reduced body mass index (BMI) and insulin response during glucose tolerance test, while increasing parent-reported physical activity and quality of life (QoL) relative to placebo.[15] In a separate placebo-controlled trial of obese adults without known hypothalamic lesions, obese patients who received long-acting octreotide lost weight and reduced their BMI compared to patients receiving placebo; post hoc analysis suggested greater effects in patients receiving the higher dose of the drug, and among "Caucasian patients having insulin secretion greater than the median of the cohort." "There were no statistically significant changes in QoL scores, body fat, leptin concentration, Beck Depression Inventory, or macronutrient intake", although patients taking octreotide had higher blood glucose after a glucose tolerance test than those receiving placebo.[19]
Octreotide has also been investigated for patients with pain from chronic pancreatitis.[20]
It has been used in the treatment of malignant bowel obstruction.[21]
Octreotide may be used in conjunction with midodrine to partially reverse peripheral vasodilation in the hepatorenal syndrome. By increasing systemic vascular resistance, these drugs reduce shunting and improve renal perfusion, prolonging survival until definitive treatment with liver transplant.[22] Similarly, octreotide can be used to treat refractory chronic hypotension.[23]
While successful treatment has been demonstrated in case reports,[24][25] larger studies have failed to demonstrate efficacy in treating chylothorax.[26]
A small study has shown that octreotide may be effective in the treatment of idiopathic intracranial hypertension.[27][28]
See also
- Octreotate, a closely related peptide
References
- ^ Official manufacturer website for up-to-date dosing & safety information: http://www.sandostatin.com
- ^ Gøtzsche PC, Hróbjartsson A (2008). "Somatostatin analogues for acute bleeding oesophageal varices". Cochrane Database Syst Rev (3): CD000193. doi:10.1002/14651858.CD000193.pub3. PMID 18677774.
- ^ Medscape: Octreoscan review
- ^ Joshua Chin, Matthew Vesnaver, Vadim Bernard-Gauthier, Erin Saucke-Lacelle, Björn Wängler, Carmen Wängler, Ralf Schirrmacher. Amino Acids: Direct one-step labeling of cysteine residues on peptides with 11C-methyl triflate for the synthesis of PET radiopharmaceuticals. Amino Acids. 2013 Aug 7. PMID 23921782
- ^ a b c d Haberfeld, H, ed. (2009). Austria-Codex (in German) (2009/2010 ed.). Vienna: Österreichischer Apothekerverlag. ISBN 3-85200-196-X.
- ^ a b c d Dinnendahl, V, Fricke, U, ed. (2010). Arzneistoff-Profile (in German) 8 (23 ed.). Eschborn, Germany: Govi Pharmazeutischer Verlag. ISBN 978-3-7741-9846-3.
- ^ Hovind P, Simonsen L, Bülow J (March 2010). "Decreased leg glucose uptake during exercise contributes to the hyperglycaemic effect of octreotide". Clin Physiol Funct Imaging 30 (2): 141–5. doi:10.1111/j.1475-097X.2009.00917.x. PMID 20132129.
- ^ Saif MW (July 2011). "Rheumatoid arthritis associated with the use of Sandostatin® LAR® depot in a patient with pancreatic neuroendocrine tumor. An association or a coincidence? The first case report". JOP 12 (4): 425–8. PMID 21737909. Lay summary – eHealthMe.com.
- ^ van der Lely AJ, de Herder WW, Lamberts SW (November 1997). "A risk-benefit assessment of octreotide in the treatment of acromegaly". Drug Saf 17 (5): 317–24. doi:10.2165/00002018-199717050-00004. PMID 9391775.
- ^ Kapicioglu S, Mollamehmetoglu M, Kutlu N, Can G, Ozgur GK (January 1998). "Inhibition of penile erection in rats by a long-acting somatostatin analogue, octreotide (SMS 201-995)". Br J Urol 81 (1): 142–5. doi:10.1046/j.1464-410x.1998.00520.x. PMID 9467491.
- ^ Klopp, T, ed. (2010). Arzneimittel-Interaktionen (in German) (2010/2011 ed.). Arbeitsgemeinschaft für Pharmazeutische Information. ISBN 978-3-85200-207-1.
- ^ Maurer R, Gaehwiler BH, Buescher HH, Hill RC, Roemer D. Opiate antagonistic properties of an octapeptide somatostatin analog. Proceedings of the National Academy of Sciences USA. 1982 Aug;79(15):4815-7. PMID 6126877
- ^ Allen MP, Blake JF, Bryce DK, Haggan ME, Liras S, McLean S, Segelstein BE. Design, synthesis and biological evaluation of 3-amino-3-phenylpropionamide derivatives as novel mu opioid receptor ligands. Bioorganic and Medicinal Chemistry Letters. 2000 Mar 20;10(6):523-6. PMID 10741545
- ^ Subcutaneous octreotide in cluster headache: randomized placebo-controlled double-blind crossover study.
- ^ a b c d Lustig RH, Hinds PS, Ringwald-Smith K, Christensen RK, Kaste SC, Schreiber RE, Rai SN, Lensing SY, Wu S, Xiong X (June 2003). "Octreotide therapy of pediatric hypothalamic obesity: a double-blind, placebo-controlled trial". J. Clin. Endocrinol. Metab. 88 (6): 2586–92. doi:10.1210/jc.2002-030003. PMID 12788859.
- ^ Flier JS (2004). "Obesity wars: Molecular progress confronts an expanding epidemic". Cell 116 (2): 337–50. doi:10.1016/S0092-8674(03)01081-X. PMID 14744442.
- ^ Boulpaep, Emile L.; Boron, Walter F. (2003). Medical physiologya: A cellular and molecular approach. Philadelphia: Saunders. p. 1227. ISBN 0-7216-3256-4.
- ^ Lustig RH (2011). "Hypothalamic obesity after craniopharyngioma: mechanisms, diagnosis, and treatment". Front Endocrinol (Lausanne) 2: 60. doi:10.3389/fendo.2011.00060. PMC 3356006. PMID 22654817.
- ^ Lustig RH, Greenway F, Velasquez-Mieyer P, Heimburger D, Schumacher D, Smith D, Smith W, Soler N, Warsi G, Berg W, Maloney J, Benedetto J, Zhu W, Hohneker J (February 2006). "A multicenter, randomized, double-blind, placebo-controlled, dose-finding trial of a long-acting formulation of octreotide in promoting weight loss in obese adults with insulin hypersecretion". Int J Obes (Lond) 30 (2): 331–41. doi:10.1038/sj.ijo.0803074. PMC 1540404. PMID 16158082.
- ^ Uhl W, Anghelacopoulos SE, Friess H, Büchler MW (1999). "The role of octreotide and somatostatin in acute and chronic pancreatitis". Digestion. 60 Suppl 2: 23–31. doi:10.1159/000051477. PMID 10207228.
- ^ Shima Y, Ohtsu A, Shirao K, Sasaki Y (May 2008). "Clinical efficacy and safety of octreotide (SMS201-995) in terminally ill Japanese cancer patients with malignant bowel obstruction". Jpn. J. Clin. Oncol. 38 (5): 354–9. doi:10.1093/jjco/hyn035. PMID 18490369.
- ^ Skagen C, Einstein M, Lucey MR, Said A (Feb 2009). "Combination Treatment With Octreotide, Midodrine, and Albumin Improves Survival in Patients With Type 1 and Type 2 Hepatorenal Syndrome.". J Clin Gastroenterol. 43 (7): 680–5. doi:10.1097/MCG.0b013e318188947c. PMID 19238094.
- ^ Patient.co.uk (Feb 2013). "Hypotension".
- ^ Kilic D, Sahin E, Gulcan O, Bolat B, Turkoz R, Hatipoglu A (2005). "Octreotide for treating chylothorax after cardiac surgery". Tex Heart Inst J 32 (3): 437–9. PMC 1336729. PMID 16392238.
- ^ Siu SL, Lam DS (2006). "Spontaneous neonatal chylothorax treated with octreotide". J Paediatr Child Health 42 (1-2): 65–7. doi:10.1111/j.1440-1754.2006.00788.x. PMID 16487393.
- ^ Chan EH, Russell JL, Williams WG, Van Arsdell GS, Coles JG, McCrindle BW (November 2005). "Postoperative chylothorax after cardiothoracic surgery in children". Ann. Thorac. Surg. 80 (5): 1864–70. doi:10.1016/j.athoracsur.2005.04.048. PMID 16242470.
- ^ Greek Researchers Investigate Octreotide Hypertension Research Foundation, accessed 2011-01-02
- ^ Panagopoulos GN, Deftereos SN, Tagaris GA, Gryllia M, Kounadi T, Karamani O, Panagiotidis D, Koutiola-Pappa E, Karageorgiou CE, Piadites G (2007). "Octreotide: a therapeutic option for idiopathic intracranial hypertension". Neurol Neurophysiol Neurosci: 1. PMID 17700925.
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Hypothalamic-pituitary hormones and analogues (H01)
|
|
| Hypothalamic |
|
GNRH
|
- Agonists: Gonadorelin
- Nafarelin
- Histrelin
Antagonists: Cetrorelix
- Ganirelix
|
|
|
Somatostatin
|
- Agonists: Lanreotide
- Octreotide
- Pasireotide
- Vapreotide
|
|
|
| Anterior pituitary |
|
ACTH
|
- Agonists: Corticotropin
- Cosyntropin
- Tetracosactide
|
|
|
GH
|
- Agonists: IGF-1 (Mecasermin/Mecasermin rinfabate)
- Sermorelin
- Somatrem
- Tesamorelin
Antagonists: Pegvisomant
|
|
|
TSH
|
|
|
|
| Posterior pituitary |
|
Oxytocin
|
- Agonists: Argiprestocin
- Aspartocin
- Carbetocin
- Cargutocin
- Demoxytocin
- Nacartocin
Antagonists: Atosiban
- Barusiban
|
|
|
Vasopressin
|
- Agonists: Argipressin
- Desmopressin
- Felypressin
- Lypressin
- Ornipressin
- Terlipressin
Antagonists: Conivaptan
- Demeclocycline
- Lixivaptan
- Mozavaptan
- Nelivaptan
- Relcovaptan
- Satavaptan
- Tolvaptan
|
|
|
|
|
|
| Description |
- Glands
- Hormones
- thyroid
- mineralocorticoids
- Physiology
- Development
|
|
| Disease |
- Diabetes
- Congenital
- Neoplasms and cancer
- Other
- Symptoms and signs
|
|
| Treatment |
- Procedures
- Drugs
- calcium balance
- corticosteroids
- oral hypoglycemics
- pituitary and hypothalamic
- thyroid
|
|
|
|
Opioidergics
|
|
Receptor
(ligands)
|
|
MOR
|
|
|
|
DOR
|
|
|
|
KOR
|
- Agonists: 6'-GNTI
- 8-CAC
- 18-MC
- 14-Methoxymetopon
- β-Chlornaltrexamine
- β-Funaltrexamine
- Adrenorphin (metorphamide)
- Akuuamicine
- Alazocine
- Allomatrine
- Asimadoline
- BAM-12P
- BAM-18P
- BAM-22P
- Big dynorphin
- Bremazocine
- BRL-52537
- Butorphanol
- BW-373U86
- Cebranopadol
- Ciprefadol
- CR845
- Cyclazocine
- Cyclorphan
- Cyprenorphine
- Diamorphine (heroin)
- Diacetylnalorphine
- Dihydroetorphine
- Dihydromorphine
- Dynorphin A
- Dynorphin B (rimorphin)
- Enadoline
- Eptazocine
- Erinacine E
- Ethylketazocine
- Etorphine
- FE 200665 (CR665)
- Fedotozine
- Fentanyl
- Gemazocine
- GR-89696
- GR-103545
- Hemorphin-4
- Herkinorin
- Hydromorphone
- HZ-2
- Ibogaine
- ICI-199,441
- ICI-204,448
- Ketamine
- Ketazocine
- Laudanosine
- Leumorphin (dynorphin B-29)
- Levallorphan
- Levorphanol
- Lofentanil
- LPK-26
- Lufuradom
- Matrine
- Menthol
- Metazocine
- Metkefamide
- Mianserin
- Mirtazapine
- Morphine
- Moxazocine
- N-MPPP
- Nalbuphine
- NalBzOH
- Nalfurafine
- Nalorphine
- Naltriben
- Norbuprenorphine
- Norbuprenorphine-3-glucuronide
- O-Desmethyltramadol
- Oripavine
- Oxilorphan
- Oxycodone
- Pentazocine
- Pethidine (meperidine)
- Phenazocine
- Proxorphan
- RB-64
- Salvinorin A (salvia)
- Salvinorin B ethoxymethyl ether
- Salvinorin B methoxymethyl ether
- SKF-10047
- Spiradoline (U-62,066)
- Thienorphine
- Tifluadom
- Tricyclic antidepressants (e.g., amitriptyline, desipramine, imipramine, nortriptyline)
- U-50,488
- U-54,494A
- U-69,593
- Xorphanol
- Antagonists: 4′-Hydroxyflavanone
- 4',7-Dihydroxyflavone
- 5'-GNTI
- 6β-Naltrexol
- 6β-Naltrexol-d4
- β-Chlornaltrexamine
- ALKS-5461
- Amentoflavone
- ANTI
- Apigenin
- Arodyne
- AT-076
- Binaltorphimine
- BU09059
- Buprenorphine
- Catechin
- Catechin gallate
- Clocinnamox
- Dezocine
- DIPPA
- Diprenorphine
- EGC
- ECG
- Epicatechin
- Hyperoside
- JDTic
- LY-255582
- LY-2196044
- LY-2456302
- LY-2459989
- LY-2795050
- Methylnaltrexone
- ML190
- ML350
- MR-2266
- Nalmefene
- Naloxone
- Naltrexone
- Naltrindole
- Naringenin
- Norbinaltorphimine
- Noribogaine
- Pawhuskin A
- PF-4455242
- Quadazocine
- Taxifolin
- UPHIT
- Zyklophin
- Unknown/unsorted: Akuammicine
- Akuammine
- Coronaridine
- Cyproterone acetate
- Dihydroakuuamine
- Ibogamine
- Tabernanthine
|
|
|
NOP
|
- Agonists: (Arg14,Lys15)Nociceptin
- ((pF)Phe4)Nociceptin(1-13)NH2
- (Phe1Ψ(CH2-NH)Gly2)Nociceptin(1-13)NH2
- Ac-RYYRWK-NH2
- Ac-RYYRIK-NH2
- Buprenorphine
- Cebranopadol
- Dihydroetorphine
- Etorphine
- MCOPPB
- MT-7716
- NNC 63-0532
- Nociceptin (orphanin FQ)
- Nociceptin (1-11)
- Nociceptin (1-13)NH2
- Norbuprenorphine
- Ro64-6198
- Ro65-6570
- SCH-221510
- SR-8993
- SR-16435
- Antagonists: (Nphe1)Nociceptin(1-13)NH2
- AT-076
- BAN-ORL-24
- J-113397
- JTC-801
- LY-2940094
- NalBzOH
- Nociceptin (1-7)
- Nocistatin
- SB-612111
- SR-16430
- Thienorphine
- Trap-101
- UFP-101
|
|
|
Unsorted /
unknown
|
- β-Casomorphins
- Amidorphin
- BAM-20P
- Cytochrophin-4
- Deprolorphin
- Gliadorphin (gluteomorphin)
- Gluten exorphins
- Hemorphins
- Kava constituents
- MEAGL
- MEAP
- NEM
- Neoendorphins
- Peptide B
- Peptide E
- Peptide F
- Peptide I
- Rubiscolins
- Soymorphins
|
|
|
Enzyme
(inhibitors)
|
|
Enkephalinase
|
- BL-2401
- Candoxatril
- D-Phenylalanine
- Ecadotril
- Kelatorphan
- Racecadotril (acetorphan)
- RB-101
- RB-120
- RB-3007
- Selank
- Semax
- Spinorphin
- Thiorphan
- Tynorphin
- Ubenimex (bestatin)
|
|
|
|
Others
|
- Propeptides: β-Lipotropin (proendorphin)
- Prodynorphin
- Proenkephalin
- Pronociceptin
- Proopiomelanocortin (POMC)
|
|
|
See also: Neuropeptidergics • Peptidergics
|
|
3. 消化管閉塞に伴う消化器症状
