ALFENTANIL

Details

Stereochemistry	ACHIRAL
Molecular Formula	C21H32N6O3
Molecular Weight	416.5172
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=IDBPHNDTYPBSNI-UHFFFAOYSA-N

InChI=1S/C21H32N6O3/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

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
Alfentanil decreases myoclonus caused by etomidate.	1999 Jun	10513376
Clinical interpretation of pharmacokinetic and pharmacodynamic propofol-opioid interactions.	2001	11799580
Choice of the hypnotic and the opioid for rapid-sequence induction.	2001	11766250
Pharmacokinetic aspects of treating infections in the intensive care unit: focus on drug interactions.	2001	11735605
Analgesic efficacy of tramadol 2 mg kg(-1) for paediatric day-case adenoidectomy.	2001 Apr	11573636
Comparison of the effects of intravenous alfentanil and esmolol on the cardiovascular response to double-lumen endobronchial intubation.	2001 Apr	11284817
A new model of electrically evoked pain and hyperalgesia in human skin: the effects of intravenous alfentanil, S(+)-ketamine, and lidocaine.	2001 Aug	11506112
Influence of pneumoperitoneum and patient positioning on respiratory system compliance.	2001 Aug	11498317
Relative sensitivity to alfentanil and reliability of current perception threshold vs von Frey tactile stimulation and thermal sensory testing.	2001 Dec	11800047
Absence of memory for intra-operative information during surgery with total intravenous anaesthesia.	2001 Feb	11573659
Gender differences in the pharmacokinetics of propofol in elderly patients during and after continuous infusion.	2001 Feb	11573657
[Epileptogenic drugs in anesthesia].	2001 Feb	11270238
Timing of pre-emptive tenoxicam is important for postoperative analgesia.	2001 Feb	11220425
Assessment of depth of anesthesia and postoperative respiratory recovery after remifentanil- versus alfentanil-based total intravenous anesthesia in patients undergoing ear-nose-throat surgery.	2001 Feb	11176083
Target-controlled alfentanil analgesia for dressing change following extensive reconstructive surgery for trauma.	2001 Jan	11302113
Remifentanil and controlled hypotension; comparison with nitroprusside or esmolol during tympanoplasty.	2001 Jan	11212044
Effect of dexmedetomidine, an alpha2-adrenoceptor agonist, on human pupillary reflexes during general anaesthesia.	2001 Jan	11167662
Myopexy (Faden) results in more postoperative vomiting after strabismus surgery in children.	2001 Jan	11152035
Comparison of five experimental pain tests to measure analgesic effects of alfentanil.	2001 Jul	11465562
Influence of pneumoperitoneum and patient positioning on preload and splanchnic blood volume in laparoscopic surgery of the lower abdomen.	2001 Jun	11435046
Concentration-effect relationship of intravenous alfentanil and ketamine on peripheral neurosensory thresholds, allodynia and hyperalgesia of neuropathic pain.	2001 Mar	11240090
The effects of chronic morphine on behavior reinforced by several opioids or by cocaine in rhesus monkeys.	2001 May 1	11295322
Neural mechanisms in the cardiovascular responses to acute central hypovolaemia.	2001 May-Jun	11428384
Comparison between dexmedetomidine and propofol for sedation in the intensive care unit: patient and clinician perceptions.	2001 Nov	11878517
Inhalation versus total intravenous anesthesia for lumbar disc herniation: comparison of hemodynamic effects, recovery characteristics, and cost.	2001 Oct	11733660
Stability of sufentanil in human plasma samples.	2001 Oct	11591902
Reexamined: the recommended endotracheal intubating dose for nondepolarizing neuromuscular blockers of rapid onset.	2001 Oct	11574363
The concentration-effect relationship of the respiratory depressant effects of alfentanil and fentanyl.	2001 Oct	11574361
The role of drug-lipid interactions on the disposition of liposome-formulated opioid analgesics in vitro and in vivo.	2001 Oct	11574359
Interaction of morphine, fentanyl, sufentanil, alfentanil, and loperamide with the efflux drug transporter P-glycoprotein.	2002 Apr	11964599
Alfentanil and sufentanil in fast-track anesthesia for coronary artery bypass graft surgery.	2002 Apr	11957163
Alfentanil-induced epileptiform activity.	2002 Feb	11903472
[Sedation analgesia in interventional radiology].	2002 Feb	11898084
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
Pharmacological treatment of postoperative shivering: a quantitative systematic review of randomized controlled trials.	2002 Feb	11812718
Pain model and fuzzy logic patient-controlled analgesia in shock-wave lithotripsy.	2002 Jan	11954700
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
Concentration-effect relationships for intravenous alfentanil and ketamine infusions in human volunteers: effects on acute thresholds and capsaicin-evoked hyperpathia.	2002 Jan	11808827
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
Total intravenous anesthesia for intraoperative monitoring of the motor pathways: an integral view combining clinical and experimental data.	2002 Mar	11883843
Implicit memory for words played during isoflurane- or propofol-based anesthesia: the lexical decision task.	2002 Mar	11873032
Prolonged neuromuscular block after rocuronium in postpartum patients.	2002 Mar	11867398
Respiratory response to skin incision during anaesthesia with infusions of propofol and alfentanil.	2002 May	12067001
Relative reinforcing effects of three opioids with different durations of action.	2002 May	11961075

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

Official Name

English

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

Systematic Name

English

ALFENTANIL [MI]

Common Name

English

R-39209-

Code

English

N-(1-(2-(4-ETHYL-4,5-DIHYDRO-5-OXO-1H-TETRAZOL-1-YL)ETHYL)-4-(METHOXYMETHYL) -4-PIPERIDINYL)-N-PHENYLPROPANAMIDE

Systematic Name

English

alfentanil [INN]

Common Name

English

RAPIFEN

Common Name

English

ALFENTANYL

Common Name

English

IDS-NA-014

Code

English

ALFENTANIL [VANDF]

Common Name

English

ALFENTANIL [HSDB]

Common Name

English

AFENTANYL

Common Name

English

Alfentanil [WHO-DD]

Common Name

English

Classification Tree Code System Code

WIKIPEDIA

List_of_fentanyl_analogues