Alfentanil hydrochloride
[CAS# 69049-06-5]

Identification

• Classification: Analytical chemistry >> Standard >> Standard material
• Name: Alfentanil hydrochloride
• Synonyms: N-[1-[2-(4-Ethyl-4,5-dihydro-5-oxo-1H-tetrazol-1-yl)ethyl]-4-(methoxymethyl)-4-piperidinyl]-N-phenylpropanamide monohydrochloride; Alfentanyl hydrochloride; R 39209
• Molecular Formula: C₂₁H₃₂N₆O₃^.HCl
• Molecular Weight: 452.98
• CAS Registry Number: 69049-06-5
• EC Number: 273-846-3
• SMILES: CCC(=O)N(C1=CC=CC=C1)C2(CCN(CC2)CCN3C(=O)N(N=N3)CC)COC.Cl

Properties

• Melting point: 140.8 ºC^*

^* "Drugs - Synonyms and Properties" data were obtained from Ashgate Publishing Co. (US)

Safety Data

• Hazard Symbols: GHS06;GHS07 Danger
• Hazard Statements: H300-H301-H301-H310-H330-H331-H336
• Precautionary Statements: P260-P261-P262-P264-P270-P271-P280-P284-P301+P316-P302+P352-P304+P340-P316-P319-P320-P321-P330-P361+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	3	H331
Acute toxicity	Acute Tox.	3	H301
Acute toxicity	Acute Tox.	2	H330
Acute toxicity	Acute Tox.	2	H300
Acute toxicity	Acute Tox.	2	H310
Specific target organ toxicity - single exposure	STOT SE	3	H336

Discovory and Applicatios

Alfentanil hydrochloride is a synthetic opioid analgesic belonging to the phenylpiperidine class, structurally related to fentanyl but characterized by a significantly shorter duration of action and faster onset. It is the hydrochloride salt form of alfentanil, developed for use in anesthesia to provide rapid and controllable analgesia. Its pharmacological profile makes it particularly suitable for short surgical procedures and as an adjunct during induction and maintenance of general anesthesia.

Alfentanil acts as a selective μ-opioid receptor agonist, producing analgesia, sedation, and respiratory depression through central nervous system binding. Compared to fentanyl, alfentanil exhibits a lower lipid solubility and higher ionization at physiological pH, contributing to its faster onset and shorter duration of effect. It is approximately one-quarter to one-tenth as potent as fentanyl by weight, but its rapid equilibration between plasma and brain results in peak effect within 1 to 2 minutes after intravenous administration.

Clinically, alfentanil hydrochloride is used for anesthesia induction in procedures requiring brief but intense analgesia. It is often administered as a bolus or as a continuous infusion to maintain a steady level of analgesia during surgery. Its rapid clearance allows for quick patient recovery and minimal residual sedation postoperatively. These features make it a preferred choice in outpatient procedures and situations requiring fast neurologic evaluation following anesthesia.

The pharmacokinetics of alfentanil are characterized by rapid distribution and elimination, with a context-sensitive half-life that remains short even during prolonged infusions. This quality differentiates it from longer-acting opioids, reducing the risk of delayed respiratory depression. Alfentanil is metabolized in the liver primarily by cytochrome P450 3A4-mediated pathways into inactive metabolites that are excreted through the kidneys.

Alfentanil hydrochloride must be administered with precision due to its potent effects on respiratory and cardiovascular systems. Dose adjustments are necessary in elderly patients and those with hepatic or renal impairment. It has minimal histamine release, which reduces the likelihood of hypotension or allergic reactions during administration, further supporting its use in patients with unstable cardiovascular status.

Despite its controlled and predictable profile, alfentanil carries the same risks as other opioids, including the potential for misuse, dependence, and respiratory depression. It is classified as a Schedule II controlled substance in the United States and similar schedules in other countries. Because of its rapid action, overdose may occur quickly, necessitating close monitoring of respiratory function and availability of opioid antagonists such as naloxone.

Alfentanil is sometimes used in intensive care units for sedation of mechanically ventilated patients, although this use is less common than with longer-acting opioids. In the operating room, it provides flexibility for anesthesiologists to titrate analgesia to rapidly changing surgical stimuli, especially in procedures like endoscopy or short general surgeries where longer-acting opioids would be less desirable.

The development of alfentanil addressed the need for ultrashort-acting opioids in surgical settings, enabling better control of anesthesia depth and more precise postoperative recovery. While its role is mainly limited to anesthetic practice, it remains a valuable agent when used by trained professionals aware of its pharmacodynamic and pharmacokinetic intricacies.

References

1990. Anesthesia for craniotomy: a double-blind comparison of alfentanil, fentanyl, and sufentanil. Anesthesiology, 73(5).
URL: https://pubmed.ncbi.nlm.nih.gov/1978615

2000. Comparison of alfentanil, fentanyl and sufentanil for total intravenous anaesthesia with propofol in patients undergoing coronary artery bypass surgery. British Journal of Anaesthesia, 85(4).
DOI: 10.1093/bja/85.4.533

2003. Alfentanil Infusion as a Component of Intravenous Anaesthesia for Coronary Artery Bypass Surgery with �Fast-track� Recovery. Anaesthesia and Intensive Care, 31(2).
DOI: 10.1177/0310057x0303100207