ALFENTANIL HYDROCHLORIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C21H32N6O3.ClH.H2O
Molecular Weight	470.993
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O.Cl.CCN1N=NN(CCN2CCC(COC)(CC2)N(C(=O)CC)C3=CC=CC=C3)C1=O

InChI

InChIKey=YYESXRRYBUERKF-UHFFFAOYSA-N

InChI=1S/C21H32N6O3.ClH.H2O/c1-4-19(28)27(18-9-7-6-8-10-18)21(17-30-3)11-13-24(14-12-21)15-16-26-20(29)25(5-2)22-23-26;;/h6-10H,4-5,11-17H2,1-3H3;1H;1H2

HIDE SMILES / InChI

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/019353s019lbl.pdf | https://www.drugbank.ca/drugs/DB00802

Alfentanil is an opioid analgesic with a rapid onset of action. Alfentanil interacts predominately with the opioid mu-receptor. These mu-binding sites are discretely distributed in the human brain, spinal cord, and other tissues. In clinical settings, alfentanil exerts its principal pharmacologic effects on the central nervous system. Its primary actions of therapeutic value are analgesia and sedation. Alfentanil may increase the patient's tolerance for pain and decrease the perception of suffering, although the presence of the pain itself may still be recognized. In addition to analgesia, alterations in mood, euphoria and dysphoria, and drowsiness commonly occur. Alfentanil depresses the respiratory centers, depresses the cough reflex, and constricts the pupils. Alfentanil, marketed under the trade name Alfenta, Rapifen in Australia is indicated for the management of postoperative pain and the maintenance of general anesthesia.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Mu opioid receptor 221 Target ID: CHEMBL233 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15694871 \| https://www.drugbank.ca/drugs/DB00802 \| https://www.ncbi.nlm.nih.gov/pubmed/16906017 \| https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/019353s021lbl.pdf	Agonist 2678

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pain 614 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/019353s019lbl.pdf	Primary		Approved 8429	ALFENTA Approved Use Alfentanil HCl injection is indicated: as an analgesic adjunct given in incremental doses in the maintenance of anesthesia with barbiturate/nitrous oxide/oxygen. as an analgesic administered by continuous infusion with nitrous oxide/oxygen in the maintenance of general anesthesia. as a primary anesthetic agent for the induction of anesthesia in patients undergoing general surgery in which endotracheal intubation and mechanical ventilation are required. as the analgesic component for monitored anesthesia care (MAC). Launch Date 1986

C_max

Value	Dose	Co-administered	Analyte	Population
20.1 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7598917	0.54 mg single, nasal dose: 0.54 mg route of administration: Nasal experiment type: SINGLE co-administered:		ALFENTANIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
1241.2 ng × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7598917	0.54 mg single, nasal dose: 0.54 mg route of administration: Nasal experiment type: SINGLE co-administered:		ALFENTANIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1985.7 ng × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7598917	0.54 mg single, intravenous dose: 0.54 mg route of administration: Intravenous experiment type: SINGLE co-administered:		ALFENTANIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
59.4 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7598917	0.54 mg single, nasal dose: 0.54 mg route of administration: Nasal experiment type: SINGLE co-administered:		ALFENTANIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
60.1 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7598917	0.54 mg single, intravenous dose: 0.54 mg route of administration: Intravenous experiment type: SINGLE co-administered:		ALFENTANIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
8% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/019353s021lbl.pdf			ALFENTANIL plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP3A5 395 CYP3A7 110

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP3A5 395	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15557344/ Page: 1.0	yes
CYP3A7 110	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15557344/ Page: 8.0	yes
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15557344/; https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/019353s023lbl.pdf Page: 1.0	yes	likely (co-administration study) Comment: Concomitant use of Alfentanil HCl Injection with a CYP3A4 inhibitor, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir), may increase plasma concentrations of Alfentanil HCl Injection; discontinuation of a CYP3A4 inducer, such as rifampin, carbamazepine, and phenytoin, in Alfentanil HCl Injection-treated patients may increase alfentanil plasma concentrations and prolong opioid adverse reactions Sources: https://pubmed.ncbi.nlm.nih.gov/15557344/; https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/019353s023lbl.pdf Page: 1.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:2569	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:2569
ZINC	ZINC000000601281	http://zinc15.docking.org/substances/ZINC000000601281

PubMed

Title	Date	PubMed
Choice of the hypnotic and the opioid for rapid-sequence induction.	2001	11766250
Effects of fentanyl, alfentanil, remifentanil and sufentanil on loss of consciousness and bispectral index during propofol induction of anaesthesia.	2001 Apr	11573626
Total intravenous anesthesia versus single breath technique and anesthesia maintenance with sevoflurane for bariatric operations.	2001 Aug	11501363
[Epileptogenic drugs in anesthesia].	2001 Feb	11270238
Comparison of effects of remifentanil and alfentanil on cardiovascular response to tracheal intubation in hypertensive patients.	2001 Jan	11575417
Effect of dexmedetomidine, an alpha2-adrenoceptor agonist, on human pupillary reflexes during general anaesthesia.	2001 Jan	11167662
Patient-controlled analgesia during SWL treatments.	2001 Jun	11465323
Influence of pneumoperitoneum and patient positioning on preload and splanchnic blood volume in laparoscopic surgery of the lower abdomen.	2001 Jun	11435046
Selective spinal anesthesia for outpatient laparoscopy. II: epinephrine and spinal cord function.	2001 Mar	11305827
Induction with propofol target-concentration infusion vs. 8% sevoflurane inhalation and alfentanil in hypertensive patients.	2001 Mar	11251433
General anaesthesia in a man with mitochondrial myopathy undergoing eye surgery.	2001 May	11350477
Auditory information processing during adequate propofol anesthesia monitored by electroencephalogram bispectral index.	2001 May	11323348
The effects of chronic morphine on behavior reinforced by several opioids or by cocaine in rhesus monkeys.	2001 May 1	11295322
Comparison between dexmedetomidine and propofol for sedation in the intensive care unit: patient and clinician perceptions.	2001 Nov	11878517
Experience with an anesthesiologist interventional model for endoscopy in a pediatric hospital.	2001 Sep	11593128
The in vitro effects of remifentanil, sufentanil, fentanyl, and alfentanil on isolated human right atria.	2001 Sep	11524316
A randomized study of the efficacy and recovery of remifentanil-based and alfentanil anaesthesia with desflurane or sevoflurane for gynecological surgery.	2002	11975425
Interaction of morphine, fentanyl, sufentanil, alfentanil, and loperamide with the efflux drug transporter P-glycoprotein.	2002 Apr	11964599
Comparison of effects of remifentanil, alfentanil and fentanyl on cardiovascular responses to tracheal intubation in morbidly obese patients.	2002 Feb	11999595
Alfentanil-induced epileptiform activity.	2002 Feb	11903472
Comparison of rocuronium and suxamethonium for rapid tracheal intubation in children.	2002 Feb	11882225
General anesthesia versus monitored anesthesia care with remifentanil for assisted reproductive technologies: effect on pregnancy rate.	2002 Feb	11880013
Concurrent ketamine and alfentanil administration: pharmacokinetic considerations.	2002 Jan	11881891
Effects of propofol and nitrous oxide on middle cerebral artery flow velocity and cerebral autoregulation.	2002 Jan	11843738
Bispectral Index (BIS) may not predict awareness reaction to intubation in surgical patients.	2002 Jan	11773816
Effects of adding alfentanil or atracurium to lidocaine solution for intravenous regional anaesthesia.	2002 Jul	12113616
Mu-receptor agonism with alfentanil increases striatal dopamine D2 receptor binding in man.	2002 Jul	12112410
Psychomotor performance after short-term anaesthesia.	2002 Jun	12094918
Postoperative nausea and vomiting after total intravenous anesthesia with propofol and remifentanil or alfentanil: how important is the opioid?	2002 Jun	12088811
Effects of remifentanil and alfentanil on the cardiovascular responses to induction of anaesthesia and tracheal intubation in the elderly.	2002 Mar	11990278
Prolonged neuromuscular block after rocuronium in postpartum patients.	2002 Mar	11867398

Patents

Sample Use Guides

In Vivo Use Guide

Spontaneously Breathing/Assisted Ventilation Induction of Analgesia: 8 to 20 mcg/kg Maintenance of Analgesia: 3 to 5 mcg/kg q 5 to 20 min or 0.5 to 1 mcg/kg/min Total dose: 8 to 40 mcg/kg Assisted or Controlled Ventilation - Assisted or Controlled Ventilation Incremental Injection (To attenuate response to laryngoscopy and intubation) Induction of Analgesia: 20 to 50 mcg/kg Maintenance of Analgesia: 5 to 15 mcg/kg q 5 to 20 min Total dose: Up to 75 mcg/kg Assisted or Controlled Ventilation - Continuous Infusion (To provide attenuation of response to intubation and incision) Induction of Analgesia: 50 to 75 mcg/kg Maintenance of Analgesia: 0.5 to 3 mcg/kg/min (Average rate 1 to 1.5 mcg/kg/min) Infusion rates are variable and should be titrated to the desired clinical effect. See Infusion Dosage Guidelines Below Total dose: Dependent on duration of procedure Anesthetic Induction Induction of Anesthesia: 130 to 245 mcg/kg Administer slowly (over 3 minutes). Maintenance of Anesthesia: 0.5 to 1.5 mcg/kg/min or general anesthetic. Infusion rates are variable and should be titrated to the desired clinical effect. See Infusion Dosage Guidelines Below Total dose: Dependent on duration of procedure At these doses truncal rigidity should be expected and a muscle relaxant should be utilized.

Route of Administration: Intravenous

In Vitro Use Guide

Alfentanil (10 uM ) significantly increased contraction of TNF-alpha and IL-1beta treated cells via a small increase in the Ca(2+) transient and a larger increase in myofilament Ca(2+) sensitivity, effects that were not blocked by 10 uM naloxone, a broad spectrum opioid receptor antagonist.

Name

Type

Language

ALFENTANIL HYDROCHLORIDE

Official Name

English

ALFENTANIL HYDROCHLORIDE [ORANGE BOOK]

Common Name

English

R 39209

Code

English

ALFENTANIL HYDROCHLORIDE [MART.]

Common Name

English

ALFENTANIL HYDROCHLORIDE [VANDF]

Common Name

English

R-39209

Code

English

PROPANAMIDE, N-(1-(2-(4-ETHYL-4,5-DIHYDRO-5-OXO-1H-TETRAZOL-1-YL)ETHYL)-4-(METHOXYMETHYL)-4-PIPERIDINYL)-N-PHENYL-, HYDROCHLORIDE, HYDRATE (1:1:1)

Systematic Name

English

ALFENTANIL HYDROCHLORIDE MONOHYDRATE

Common Name

English

ALFENTANIL HYDROCHLORIDE MONOHYDRATE [MI]

Common Name

English

ALFENTANIL HYDROCHLORIDE [USAN]

Common Name

English

ALFENTANIL HYDROCHLORIDE [USP MONOGRAPH]

Common Name

English

ALFENTANIL HYDROCHLORIDE [EP IMPURITY]

Common Name

English

R-39,209

Code

English

N-[1-[2-(4-Ethyl-5-oxo-2-tetrazolin-1-yl)-ethyl]-4-(methoxymethyl)-4-piperidyl]propionanilide monohydrochloride monohydrate

Systematic Name

English

PROPANAMIDE, N-(1-(2-(4-ETHYL-4,5-DIHYDRO-5-OXO-1H-TETRAZOL-1-YL)ETHYL)-4-(METHOXYMETHYL)-4-PIPERIDINYL)-N-PHENYL, MONOHYDROCHLORIDE, MONOHYDRATE

Common Name

English

R 39,209

Code

English

ALFENTANIL HYDROCHLORIDE [USP IMPURITY]

Common Name

English

ALFENTA

Brand Name

English

ALFENTANIL HYDROCHLORIDE [USP-RS]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1506