Women had slower gastric emptying rates than men according to a study of 20 men and 40 women. Premenopausal women, postmenopausal women, and postmenopausal women taking oral estrogen had slower gastric emptying than men. The antrum is the part of the stomach located near the entrance to the small bowel.  Antral motility was measured during this study, and there was no difference between men and women.

Source:
Influence of gender and menopause on gastric emptying and motility.
Hutson WR, Roehrkasse RL, and Wald A. Gastroenterology. 1989 Jan;96(1):11-7.

A seperate study compared premenopausal women to age matched men. Their rate to empty half their gastric contents was thirty minutes longer than men. Dynamic antral scintigraphy uses nuclear medicine to measure to contractions in the antrum. Using this technique, the contractility of the mid-antrum was shown to be significantly lower in women.

Source:
Knight LC, Parkman HP, Brown KL, Miller MA, Trate DM, Maurer AH, and Fisher RS. Delayed gastric emptying and decreased antral contractility in normal premenopausal women compared with men. Am J Gastroenterol. 1997 Jun;92(6):968-75.

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Opiates such as morphine can delay gastric emptying and intestinal transit.

Source:

Wood JD, and Galligan JJ. Function of opioids in the enteric nervous system. Neurogastroenterol Motil. 2004;16 Suppl 2:17-28.

Methylnalrexone is mu-opioid receptor antagonist which does not cross the blood brain barrier. It has been shown in a randomized  study of 133 patients to induce defecation rapidly without reversing the central analgesic effects of opioids.

Source:

Thomas J, Karver S, Cooney GA, Chamberlain BH, Watt CK, Slatkin NE, Stambler N, Kremer AB, and Israel RJ. Methylnaltrexone for opioid-induced constipation in advanced illness. N Engl J Med. 2008 May 29;358(22):2332-43.

In a randomized, double-blind, crossover placebo-controlled study, analysis of patients  given morphine or morphine and methylnaltrexone showed a reversal of the delay in gastric emptying.

Source:

Murphy DB, Sutton JA, Prescott LF, and Murphy MB. Opioid-induced delay in gastric emptying: a peripheral mechanism in humans. Anesthesiology. 1997 Oct;87(4):765-70.

Methylnaltrexone was not shown to prevent post-operative nausea and vomiting in a  prospective double-blind trial.

Source:

Moerman I, Franck P, and Camu F. Evaluation of methylnaltrexone for the reduction of postoperative vomiting and nausea incidences. Acta Anaesthesiol Belg. 1995;46(3-4):127-32.

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TZP-102 is an oral ghrelin receptor agonist which recently underwent a phase 2a randomized, double-blind trial with 92 patients showing no significant improvement in gastric emptying but did provide symptomatic relief.  Other trials have also had no improvement in gastric emptying but symptom improvement.

Source:

Ejskjaer N, Wo JM, Esfandyari T, Mazen Jamal M, Dimcevski G, Tarnow L, Malik RA, Hellström PM, Mondou E, Quinn J, Rousseau F, and McCallum RW. A phase 2a, randomized, double-blind 28-day study of TZP-102 a ghrelin receptor agonist for diabetic gastroparesis. Neurogastroenterol Motil. 2013;25(2):e140-50.

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Among ten patients with diabetic and idiopathic gastroparesis, erythromycin was shown to decrease symptoms and gastric emptying time with both  oral and intravenous forms.

Source:
Richards RD, Davenport K, and McCallum RW. The treatment of idiopathic and diabetic gastroparesis with acute intravenous and chronic oral erythromycin. Am J Gastroenterol. 1993 Feb;88(2):203-7.

Six patients given intravenous erythromycin for post-vagotomy-antrectomy gastroparesis showed improvement in initial phase of solid meal gastric emptying.

Source:

Kendall BJ, Chakravarti A, Kendall E, Soykan I, and McCallum RW. The effect of intravenous erythromycin on solid meal gastric emptying in patients with chronic symptomatic post-vagotomy-antrectomy gastroparesis. Aliment Pharmacol Ther. 1997 Apr;11(2):381-5.

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In a retrospective study of 24 diabetic patients with nausea and vomiting who failed prokinetics, tricyclic antidepressant therapy showed symptomatic improvement .

Source:

Sawhney M, Prakash C, Lustman P, and Clouse R. Tricyclic antidepressants for chronic vomiting in diabetic patients. Dig Dis Sci. 2007;52(2):418-24.

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Aprepitant is a medication available for nausea and vomiting.  Most clinical trials were to prevent nausea and vomiting from chemotherapy.

Based on retrospective data, 42 patients treated with aprepitant and granisetron had a higher rate of complete response than 40 patients treated only with granisetron without significant difference in adverse drug events.

Source:

Uchida M, Ikesue H, Kato K, Ichinose K, Hiraiwa H, Sakurai A, Takenaka K, Iwasaki H, Miyamoto T, Teshima T, Egashira N, Akashi K, and Oishi R. Antiemetic effectiveness and safety of aprepitant in patients with hematologic malignancy receiving multiday chemotherapy. Am J Health Syst Pharm. 2013;70(4):343-9.

Animal models have shown high levels of substance P in the area postrema and the vagal afferents.

Sources:

Paasonen M and Vogt M. The effect of drugs on the amounts of substance P and 5-hydroxytryptamine in mammalian brain. J Physiol. 1956; 131(3): 617–626.
Amin A, Crawford T, and Gaddum J. The distribution of substance P and 5-hydroxytryptamine in the central nervous system of the dog. J Physiol. 1956;126:596–618.

The action of substance P in these centers is controlled by the neurokinin-1 receptor and antagonism of this receptor has shown anti-emetic activity in animals given cisplatin. CNS penetration is required for antiemetic action.

Source:
Tattersall FD, Rycroft W, Francis B, Pearce D, Merchant K, MacLeod AM, Ladduwahetty T, Keown L, Swain C, Baker R, Cascieri M, Ber E, Metzger J, MacIntyre DE, Hill RG, and Hargreaves RJ. Tachykinin NK1 receptor antagonists act centrally to inhibit emesis induced by the chemotherapeutic agent cisplatin in ferrets. Neuropharmacology. 1996;35(8):1121-9.

Aprepitant  is a selective, oral nonpeptide antagonist of the NK1 receptor with the ability to penetrate the central nervous system. The earliest clinical trials were for patients receiving chemotherapy, specifically cisplatin. In a randomized,  double-blind, placebo-controlled phase III study of 520 patients, 72.7% of the patients receiving aprepitant, 5-HT3 antagonist and steroids had complete response (no emesis and no rescue therapy) versus 52.3% in the standard therapy group receiving 5-HT3 antagonist and steroids.

Source:
Hesketh PJ, Grunberg SM, Gralla RJ, Warr DG, Roila F, de Wit R, Chawla SP, Carides AD, Ianus J, Elmer ME, Evans JK, Beck K, Reines S, and Horgan KJ;.The oral neurokinin-1 antagonist aprepitant for the prevention of chemotherapy-induced nausea and vomiting: a multinational, randomized, double-blind, placebo-controlled trial in patients receiving high-dose cisplatin–the Aprepitant Protocol 052 Study Group. J Clin Oncol. 2003;21(22):4112-9. Epub 2003 Oct 14.

Two case reports are available for the use of aprepitant for gastroparesis. It is available in the United States for nausea and vomiting associated with chemotherapy and surgery. One patient with refractory idiopathic gastroparesis responded to aprepitant 40 mg daily.

Source:

Fahler J, Wall GC, and Leman BI. Gastroparesis-associated refractory nausea treated with aprepitant. Ann Pharmacother. 2012 Dec;46(12):e38.

Another patient with refractory diabetic gastroparesis was able to tolerate aprepitant for four months prior to gastric electrical stimulation device placement.

Source:

Chong K, and Dhatariya K. A case of severe, refractory diabetic gastroparesis managed by prolonged use of aprepitant. Nat Rev Endocrinol. 2009 ;5(5):285-8.

Clinical trial for gastroparesis and aprepitant.

[url]http://clinicaltrial.gov/ct2/show/NCT01149369[/url]

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Prucalopride is a medication which can be used for constipation. It is a selective, high-affinity 5-HT4 receptor agonist shown to improve spontaneous complete bowel movements in a randomized, placebo controlled double-blind trial of 713 patients with constipation.

Source:

Tack J, van Outryve M, Beyens G, Kerstens R, and Vandeplassche L. Prucalopride (Resolor) in the treatment of severe chronic constipation in patients dissatisfied with laxatives. Gut. 2009;58(3):357-65.

Prucalopride showed no difference between placebo for corrected QT intervals or incidence of supraventricular or ventricular arrythmias in a phase II trial among elderly patients with constipation.

Source:
Camilleri M, Beyens G, Kerstens R, Robinson P, and Vandeplassche L. Safety assessment of prucalopride in elderly patients with constipation: a double-blind, placebo-controlled study. Neurogastroenterol Motil. 2009;21(12):1256-e117.

Prucalopride does not affect the hERG potassium channel. Cisapride did affect this cardiac channel and could have induced arrhythmias. No significant data is available for the use of prucalopride for gastroparesis.

Source:
QuigleyM. Prucalopride: safety, efficacy and potential applications. Therap Adv Gastroenterol. 2012; 5(1): 23–30.

Two patients with scleroderma were reported to have symptomatic improvement after treatment with prucalopride.

Source:

Boeckxstaens GE, Bartelsman JF, Lauwers L, and Tytgat GN. Treatment of GI dysmotility in scleroderma with the new enterokinetic agent prucalopride. Am J Gastroenterol. 2002;97(1):194-7.

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Chronic marijuana use can lead to cannabis hyperemesis syndrome characterized by unexplained recurrent nausea and vomiting, compulsive bathing, abdominal pain, and polydypsia. In a report of eight cases, patients developed the syndrome after 19 years of use. The majority of people who stop using marijuana have symptom improvement.

Source: Soriano-Co M, Batke M, and Cappell MS. The cannabis hyperemesis syndrome characterized by persistent nausea and vomiting, abdominal pain, and compulsive bathing associated with chronic marijuana use: a report of eight cases in the United States. Dig Dis Sci. 2010;55(11):3113-9.

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Cannabinoids are marijuana base medications. They can be used to control nausea and vomiting. The earliest studies were from the 1980s and compared them to prochlorperazine. In 1985, nabilone was compared to prochlorperazine for chemotherapy related emesis and was shown to be significantly superior in reducing   vomiting episodes.

Source:

Niiranen A, and Mattson K. A cross-over comparison of nabilone and prochlorperazine for emesis induced by cancer chemotherapy. Am J Clin Oncol. 1985;8(4):336-40.

More recently, dronabinol was compared to ondansetron for delayed chemotherapy-induced nausea and vomiting. Among 61 patients, dronabinol and ondansetron were equally effective by themselves. Combination therapy was not superior.

Source:

Meiri E, Jhangiani H, Vredenburgh JJ, Barbato LM, Carter FJ, Yang HM, and Baranowski V.  Efficacy of dronabinol alone and in combination with ondansetron versus ondansetron alone for delayed chemotherapy-induced nausea and vomiting. Curr Med Res Opin. 2007;23(3):533-43.

Dronabinol is available in the United States and most patients respond to 5mg orally three times a day.

[url]http://www.fda.gov/ohrms/dockets/dockets/05n0479/05N-0479-emc0004-04.pdf[/url]

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Metoclopramide is a medication for nausea and vomiting. It can be used for gastroparesis.

After FDA approval in 1979, a study in 1985 showed that gastric emptying improvement did not correlate with symptom improvement. Metoclopramide is thought to work through both prokinetic and anti-emetic effects.

Source:
Ricci DA, Saltzman MB, Meyer C, Callachan C, and McCallum RW. Effect of metoclopramide in diabetic gastroparesis. J Clin Gastroenterol. 1985;7(1):25-32.

In a trial of ten patients, metoclopramide had a significantly higher rate of improving gastric emptying versus placebo. However gastric emptying could not correlate with symptom improvement.

Source:
Snape WJ Jr, Battle WM, Schwartz SS, Braunstein SN, Goldstein HA, and Alavi A. Metoclopramide to treat gastroparesis due to diabetes mellitus: a double-blind, controlled trial. Ann Intern Med. 1982;96(4):444-6.

A trial of ten patients showed outpatient subcutaneous metoclopramide administration can lead to improvement in gastric emptying and symptoms.  In the outpatient setting, subcutaneous metoclopramide can be used as an adjunct to the patient’s oral medication.

Source:
McCallum RW, Valenzuela G, Polepalle S, and Spyker D. Subcutaneous metoclopramide in the treatment of symptomatic gastroparesis: clinical efficacy and pharmacokinetics. J Pharmacol Exp Ther. 1991;258(1):136-42.

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