Nalorphine

Not to be confused with Nalbuphine.

Nalorphine (INNTooltip International Nonproprietary Name; also known as N-allylnormorphine; brand names Lethidrone and Nalline) is a mixed opioid agonist–antagonist with opioid antagonist and analgesic properties.^[2] It was introduced in 1954^[3] and was used as an antidote to reverse opioid overdose and in a challenge test to determine opioid dependence.^[4]

Nalorphine

Clinical data
Trade names	Lethidrone, Nalline
Other names	N-Allylnormorphine
AHFS/Drugs.com	International Drug Names
ATC code	V03AB02 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) BR: Class A2 (Narcotic drugs)[1] CA: Schedule I US: Schedule III
Identifiers
IUPAC name 17-allyl-7,8-didehydro-4,5α-epoxymorphinan-3,6α-diol
CAS Number	62-67-9 Y
PubChem CID	5284595
IUPHAR/BPS	1629
DrugBank	DB11490 Y
ChemSpider	4447643 Y
UNII	U59WB2WRY2
KEGG	D08247
ChEBI	CHEBI:7458
ChEMBL	ChEMBL415284 Y
CompTox Dashboard (EPA)	DTXSID3023348
ECHA InfoCard	100.000.497
Chemical and physical data
Formula	C19H21NO3
Molar mass	311.381 g·mol−1
3D model (JSmol)	Interactive image
SMILES O[C@@H]1[C@@H]2OC3=C4C(C[C@H]5N(CC[C@]42[C@@]5([H])C=C1)CC=C)=CC=C3O
InChI InChI=1S/C19H21NO3/c1-2-8-20-9-7-19-12-4-6-15(22)18(19)23-17-14(21)5-3-11(16(17)19)10-13(12)20/h2-6,12-13,15,18,21-22H,1,7-10H2/t12-,13+,15-,18-,19-/m0/s1 Y Key:UIQMVEYFGZJHCZ-SSTWWWIQSA-N Y
(verify)

Nalorphine was the second opioid antagonist to be introduced, preceded by nalodeine (N-allylnorcodeine) in 1915 and followed by naloxone in 1960 and naltrexone in 1963.^[3] Due to potent activation of the κ-opioid receptor, nalorphine produces side effects such as dysphoria, anxiety, confusion, and hallucinations, and for this reason, is no longer used medically.^[2][3][5]

Pharmacology

Pharmacodynamics

Nalorphine acts at two opioid receptors — the μ-opioid receptor (MOR) where it has antagonistic effects, and at the κ-opioid receptor (KOR) (K_i = 1.6 nM; EC₅₀ = 483 nM; E_max = 95%) where it exerts high-efficacy partial agonist/near-full agonist characteristics.^[6]

Chemistry

Analogues

Nalorphine has a number of analogues including niconalorphine (the nicomorphine analogue), diacetylnalorphine (heroin analogue), dihydronalorphine (dihydromorphine), and a number of others as well as a number of codeine-based analogues.^[7]

Synthesis

Nalorphine synthesis:^[8] amended procedure:^[9][10][11]

More recently, it has become much more commonplace to use ethyl chloroformate instead of cyanogen bromide for the Von Braun degradation demethylation step. See for example the list of phenyltropanes or the synthesis of paroxetine for further examples of this.

See also

• Diacetylnalorphine
• Levallorphan
• Nalbuphine
• Nalorphine dinicotinate