Metoclopramide hydrochloride
[CAS# 7232-21-5]

Identification

• Classification: API >> Digestive system medication >> Gastrointestinal motility drugs
• Name: Metoclopramide hydrochloride
• Synonyms: 4-Amino-5-chloro-N-[2-(diethylamino)ethyl]-2-methoxybenzamide monohydrochloride
• Molecular Formula: C₁₄H₂₂ClN₃O₂^.HCl
• Molecular Weight: 336.26
• CAS Registry Number: 7232-21-5
• EC Number: 230-634-5
• SMILES: CCN(CC)CCNC(=O)C1=CC(=C(C=C1OC)N)Cl.Cl

Properties

• Solubility: soluble H2O (Expl.)

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302
• Precautionary Statements: P264-P270-P301+P317-P330-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319
Specific target organ toxicity - single exposure	STOT SE	3	H335

Discovory and Applicatios

Metoclopramide hydrochloride is a widely used pharmaceutical agent primarily classified as a prokinetic and antiemetic drug. It was first synthesized and introduced in the mid-20th century to manage gastrointestinal disorders involving delayed gastric emptying and to prevent nausea and vomiting.

Pharmacologically, metoclopramide hydrochloride acts mainly as a dopamine D₂ receptor antagonist in the central nervous system and gastrointestinal tract. By blocking dopamine receptors in the chemoreceptor trigger zone of the brain, it prevents nausea and vomiting. In the gastrointestinal tract, dopamine receptor blockade enhances acetylcholine release, which increases gastric motility and accelerates gastric emptying without stimulating gastric acid secretion.

Clinically, metoclopramide hydrochloride is used for the treatment of gastroparesis, a condition characterized by delayed gastric emptying often seen in diabetic patients. It is also prescribed for gastroesophageal reflux disease (GERD) to improve esophageal motility and lower esophageal sphincter tone. Additionally, it is widely used to prevent and treat nausea and vomiting caused by chemotherapy, radiation therapy, surgery, or migraine headaches.

Metoclopramide hydrochloride is available in oral, intravenous, and intramuscular formulations, providing flexibility depending on the clinical setting. Oral administration is commonly used for chronic management, while parenteral forms are preferred for acute or severe symptoms.

Pharmacokinetically, metoclopramide hydrochloride is rapidly absorbed after oral administration, reaching peak plasma concentrations within 1 to 2 hours. It undergoes partial metabolism in the liver, with approximately 85% excreted unchanged in the urine. The elimination half-life ranges from 5 to 6 hours, supporting multiple daily dosing.

Adverse effects of metoclopramide hydrochloride are mainly related to its central nervous system activity and include drowsiness, fatigue, restlessness, and extrapyramidal symptoms such as dystonia, akathisia, and tardive dyskinesia, especially with prolonged use or high doses. These neurological effects result from dopamine receptor blockade in the basal ganglia. Due to these risks, its long-term use is generally limited, and caution is advised in certain populations.

Metoclopramide hydrochloride also exhibits some serotonergic effects by acting as a 5-HT₃ receptor antagonist and 5-HT₄ receptor agonist, which contribute to its prokinetic and antiemetic properties.

In summary, metoclopramide hydrochloride is an effective dopamine receptor antagonist with prokinetic and antiemetic effects used to treat gastrointestinal motility disorders and prevent nausea and vomiting. Its pharmacological profile and clinical utility have made it a valuable drug in both acute and chronic care, with attention needed to manage and monitor potential neurological side effects.

References

1979. Striatal DOPAC elevation predicts antipsychotic efficacy of metoclopramide. Life Sciences, 24(20).
DOI: 10.1016/0024-3205(79)90243-1

1991. Metoclopramide-Induced Acute Congestive Heart Failure. Southern Medical Journal, 84(2).
DOI: 10.1097/00007611-199102000-00041

2023. Effects of different auricular point therapies on digestive symptoms and quality of life in patients undergoing platinum-based chemotherapy. Journal of Acupuncture and Tuina Science, 21(5).
DOI: 10.1007/s11726-023-1396-y