71195-58-9 Usage
Uses
The low pKa of alfentanil (6.9) results in it being largely unionised at plasma
pH, allowing rapid diffusion to the effect site (t1.2keo ~1min) and rapid onset
of action despite it being less lipid soluble than other opioids. It does not bind strongly to opioid receptors, and the effect-site concentration also
decreases rapidly as plasma concentrations decrease. Alfentanil is
metabolised by the hepatic cytochrome P450 isoform CYP3A4. Genetic
variability in the activity of this enzyme may result in two- to threefold
variations in pharmacokinetic values when given by infusion. Low, medium
or high metabolisers have been identified; this has implications for duration
of action when prolonged use is contemplated.
Definition
ChEBI: A member of the class of piperidines that is piperidine having a 2-(4-ethyl-5-oxo-4,5-dihydro-1H-tetrazol-1-yl)ethyl group at the 1-position as well as N-phenylpropanamido- and methoxymethyl groups at the 4-position.
General Description
The addition of a methoxy methyl on the 4-piperidine and thesubstitution of the phenethyl ring for an ethyl-substitutedtetrazole-one yielded a compound with about one fourth toone third the potency of fentanyl. Although lesspotent, it has a quicker onset of action, a shorter duration ofaction, and thus a better, safety profile for use as an anestheticadjunct. The piperidine amine has a pKa of 6.5 compared withfentanyl’s pKa of 8.4. This results in a higher proportion ofunionized drug for alfentanil leading to quicker penetrationthrough the blood-brain barrier and thus onset of action.Alfentanil (Alfenta) is available as an IV injection for use asan analgesic adjunct for induction of general anesthesia and tomaintain analgesia during general surgical procedures.
Clinical Use
Opioid analgesic:
Short surgical procedures
Intensive care sedation
Drug interactions
Potentially hazardous interactions with other drugs
Antibacterials: concentration increased by
erythromycin; metabolism accelerated by rifampicin.
Antidepressants: possible CNS excitation or
depression (hypertension or hypotension) in patients
also receiving MAOIs (including moclobemide)
- avoid; possibly increased sedative effects with
tricyclics.
Antifungals: metabolism inhibited by fluconazole
and ketoconazole (risk of prolonged or delayed
respiratory depression); metabolism possibly
inhibited by itraconazole; concentration increased by
voriconazole, consider reducing alfentanil dose.
Antihistamines: increased sedative effects with
sedating antihistamines.
Antipsychotics: enhanced hypotensive and sedative
effects.
Antivirals: concentration possibly increased by
ritonavir; increased risk of ventricular arrhythmias
with saquinavir - avoid.
Cytotoxics: use crizotinib with caution.
Dopaminergics: avoid with selegiline.
Sodium oxybate: enhanced effect of sodium oxybate
- avoid.
Metabolism
Alfentanil is metabolised in the liver; oxidative N- and
O-dealkylation by the cytochrome P450 isoenzyme
CYP3A4 leads to inactive metabolites, which are excreted
in the urine.
Check Digit Verification of cas no
The CAS Registry Mumber 71195-58-9 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 7,1,1,9 and 5 respectively; the second part has 2 digits, 5 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 71195-58:
(7*7)+(6*1)+(5*1)+(4*9)+(3*5)+(2*5)+(1*8)=129
129 % 10 = 9
So 71195-58-9 is a valid CAS Registry Number.
71195-58-9Relevant articles and documents
SUBSTITUTED 4-AMINO-PIPERIDINES
-
Page/Page column 31, (2010/02/17)
The present invention relates to new substituted 4-amino-piperidine opioid receptor modulators, pharmaceutical compositions thereof, and methods of use thereof
Synthetic 1,4-Disubstituted-1,4-dihydro-5H-tetrazol-5-one Derivatives of Fentanyl: Alfentanil (R 39209), a Potent, Extremely Short-Acting Narcotic Analgesic
Janssens, Frans,Torremans, Joseph,Janssen, Paul A.J.
, p. 2290 - 2297 (2007/10/02)
The synthesis of a series of N-1,4-disubstituted-1,4-dihydro-5H-tetrazol-5-one piperidinyl derivatives of fentanyl (10), carfentanil (11), and sufentanil (12) is described.The 1-substituted tetrazolinones 2 were essentially prepared via the addition reaction of aluminum azide to isocyanates or acid chlorides in tetrahydrofuran.Alkylation of 2 under neutral or weakly basic conditions afforded almost exclusively the 1,4-disubstituted tetrazolinone isomer 3.N-Alkylation of the piperidine derivatives 4 with 3 in dimethylformamide yielded 9a-v.The morphinomimetic activity in rats, after intravenous injection of the compounds, was evaluated in the tail withdrawal reflex test.The fentanyl analogues 9a-c (R4 = H) are inactive at the measured dose of 2.5 or 10 mg/kg (iv).For the carfentanil analogues (R4 = COOCH3) maximal narcotic activity is found when R1 represents a lower alkyl group (9d-f) or a thienylethyl group (9n).The sufentanil analogues (R4 = CH2OCH3) show the same structure-activity relationship (SAR) profile as the carfentanil derivatives (R4 = COOCH3).The structural requirements for optimal activity are in good agreement with earlier observations in the series of 10-12.From the series the ethyl tetrazolinone derivative 9r, alfentanil (R 39209), was selected for clinical investigation.As an analgesic in rats, 9r is 140 times more potent then pethidine 15 and 72 times more potent than morphine 14.Alfentanil reaches its peak effect within 1 min after injection, and its duration of action is very short; at 2 times its MED50, 9r has a duration of action of 11 min.This duration is 30 min for 10 and 90 min for 14.Compared to 10, alfentanil 9r is about 4 times faster but 3 times shorter acting.Structurally, 9r shows most resemblance to sufentanil 12, since it differs only by substitution of a 4-ethyltetrazolinone ring for the thiophene ring.The considerable differences in their pharmacological profiles were explained in terms of marked variations in physicochemical and, hence, pharmacokinetic properties.
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