Demerol
Marquetta Allen
Karen Dwelley
Demerol is an opioid agonist and a Schedule II controlled substance with an abuse liability
similar to morphine.1 It is also referred to as isonipecaine, lidol, pethanol, piridosal, Algil,
Alodan, Centralgin, Dispadol, Dolantin, Mialginis, Petidin Dolargan, Dolestine, Dolosal, Dolsin,
Mefedina.2 Meperidine is the active ingredient in Demerol and is recommended for relief of
moderate to severe pain.3 The usual dosage for pediatric patients is 1.1 mg/kg to 1.8 mg/kg
orally, up to the adult dose, every 3 or 4 hours as necessary. The usual dosage for adults is 50
mg to 150 mg orally, every 3 or 4 hours as necessary and for preoperative use (with injectable
Demerol) is 50 mg to 100 mg given 30 to 60 minutes before anesthesia. During labor,
recommended dose is 50 - 100 mg injected intramuscularly or subcutaneously once pain
becomes regular.4 Dizziness, lowered blood pressure, shallow breathing, sedation, nausea,
disorientation, dry mouth, itchiness, sweating, constipation, and skin rash are some side effects
of Demerol. Other serious side effects include respiratory arrest, cardiac arrest, hallucinations
and severe convulsions and can be highly addictive.5
Scheme 1: Chemical structure of Demerol
1 Sanofi-Aventis, www.products.sanofi-aventis.us/demerol/demerol.pdf (accessed March, 2, 2010).
2 Wikipedia, http://en.wikipedia.org/wiki/Pethidine (accessed March 2, 2010).
3 DrugLib, http://www.druglib.com/activeingredient/meperidine/ (accessed March 1, 2010).
4 Medtv, http://pain.emedtv.com/demerol/demerol-dosage.html (accessed March 3, 2010).
5 Scripts RX, http://www.scriptsrehab.com/di-demerol.htm (accessed March 3, 2010).
Demerol
1H NMR (free base): δ 7.47 (d, J = 2.4 Hz, 1H), 7.39 (d, J = 8.4 Hz, 1H), 7.23 (dd, J = 2.0 Hz, J = 8.4 Hz, 1H), 4.04 (t, J =
6.6 Hz, 2H), 2.79 (br s, 2H), 2.56 (d, J = 13.2 Hz, 2H), 2.28 (s, 3H), 2.16 (m, 2H), 1.96 (m, 2H), 1.59 (m, 2H), 0.86 (t, J =
7.6 Hz, 3H).6
13C NMR (free base): δ 173.5, 136.6, 131.2, 130.4, 128.2, 125.4, 66.8, 53.2, 48.3, 46.1, 33.6, 21.8, 10.3. Anal. Calcd
for C16H21NO2Cl2·HCl·H2O: C, 49.95; H, 6.29; N, 3.64. Found: C, 50.19; H, 6.00; N, 3.70. 7
Figure 1. Mass Spectum of Meperidine (EI, from the National Institute of Standards and Technology8)
6 Lomenzo et al. Synthesis and Biological Evaluation of Meperidine Analogues at Monoamine
Transporters. J. Med. Chem. 2005, 1336-1338.
7 Wikipedia, http://en.wikipedia.org/wiki/Pethidine (accessed March 5, 2010).
8
NIST Chemistry WebBook, http://webbook.nist.gov/cgi/cbook.cgi?Spec=C57421&Index=0& Type=Mass
(accessed March 5, 2010).
Demerol
There are many different ways to synthesize Meperidine, the active ingredient in Demerol. In
past years before Meperidine introduced Pethidine was well known for its potent pain relieving
activity. The 4-phenylpiperidine compound originally had the formula of an alkoxyaryl, with
diphenylmethoxy group.9 The more recent way of synthesizing the drug is through a generic
approach by aryl-substituted derivatives. That simply means converting the nitriles in the form
N-methyl-4-aryl-4-poperidine-4-carbonitriles to ethyl esters, or synthesizing a methyl or a
halogen group along with the phenol of the structure. Synthesizing a methyl or a halogen
group along with the phenol basically increases the affinity of where and what sites in the body
Meperidine will be transported to when it enters the brain.10 The transporters that carry
Meperidine to the sites are commonly referred to as DAT or the dopamine transporter, NET the
norepinephrine transporter, and SERT the serotonin transporter.11
Scheme 2: Reagents and conditions: (a) BrCH2CH(OCH3)2, NaNH2, toluene. (b) 3N HCl, 50 °C, 4.5 h. (c)
CH3NH2•HCl, CH3OH, NaBH3CN. (d) H2SO4/H2O 120 °C; then EtOH, azeotropic distillation.
9 Eisleb, O. New Synthesis of Sodium Amide. Berichte 1941, pp 2-3.
10 Lomenzo et al. Synthesis and Biological Evaluation of Meperidine Analogues at Monoamine
Transporters. J. Med. Chem., 2005, 1336-1338.
11 Shevd, K. Low-dose intrathecal meperidine for lower limb surgery. Can. J. Anesthesia 2005, 26-27.