DrugBank: Pentazocine (DB00652)

targets (3)

Identification

Name

Pentazocine

Accession Number

DB00652 (APRD01173)

Type

small molecule

Groups

approved

Description

The first mixed agonist-antagonist analgesic to be marketed. It is an agonist at the kappa and sigma opioid receptors and has a weak antagonist action at the mu receptor. (From AMA Drug Evaluations Annual, 1991, p97)

Structure

Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure

Synonyms

L-pentazocine
Pentazocaine
Pentazocin

Brand names

Fortalgesic
Fortalin
Fortral
Liticon
Pentagin
Soseton
Sosigon
Talwan

Brand name mixtures

Talacen (pentazocine + acetaminophen)
Talwin (pentazocine + naloxone)

Categories

Narcotics
Adjuvants, Anesthesia
Analgesics, Opioid
Narcotic Antagonists

CAS number

359-83-1

Weight

Average: 285.4238
Monoisotopic: 285.209264491

Chemical Formula

C₁₉H₂₇NO

InChI Key

InChIKey=VOKSWYLNZZRQPF-GDIGMMSISA-N

InChI

InChI=1S/C19H27NO/c1-13(2)7-9-20-10-8-19(4)14(3)18(20)11-15-5-6-16(21)12-17(15)19/h5-7,12,14,18,21H,8-11H2,1-4H3/t14-,18+,19+/m0/s1

Plain Text

IUPAC Name

(1R,9R,13R)-1,13-dimethyl-10-(3-methylbut-2-en-1-yl)-10-azatricyclo[7.3.1.0^{2,7}]trideca-2,4,6-trien-4-ol

SMILES

C[C@H]1[C@H]2CC3=CC=C(O)C=C3[C@]1(C)CCN2CC=C(C)C

Plain Text

Mass Spec

Not Available

Taxonomy

Kingdom

Organic

Classes

Morphinans

Substructures

Morphinans
Hydroxy Compounds
Alkanes and Alkenes
Naphthalenes
Phenols and Derivatives
Benzene and Derivatives
Phenylpiperidines
Aliphatic and Aryl Amines
Phenethylamines
Heterocyclic compounds
Aromatic compounds
Phenylpropylamines
Cyclohexenes and Derivatives
Phenyl Esters
Amphetamines
Piperidines

Pharmacology

Indication

For the relief of moderate to severe pain.

Pharmacodynamics

Pentazocine is a potent analgesic which when administered orally in a 50 mg dose appears equivalent in analgesic effect to 60 mg (1 grain) of codeine. Onset of significant analgesia usually occurs between 15 and 30 minutes after oral administration, and duration of action is usually three hours or longer. Onset and duration of action and the degree of pain relief are related both to dose and the severity of pretreatment pain. Pentazocine weakly antagonizes the analgesic effects of morphine and meperidine; in addition, it produces incomplete reversal of cardiovascular, respiratory, and behavioral depression induced by morphine and meperidine. Pentazocine has about 1/50 the antagonistic activity of nalorphine. It also has sedative activity.

Mechanism of action

The preponderance of evidence suggests that pentazocine antagonizes the opioid effects by competing for the same receptor sites, especially the opioid mu receptor.

Absorption

Well absorbed from the gastro-intestinal tract.

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

Hepatic

Route of elimination

Not Available

Half life

2 to 3 hours

Clearance

Not Available

Toxicity

Not Available

Affected organisms

Humans and other mammals

Pathways

Not Available

Pharmacoeconomics

Manufacturers

Sanofi aventis us llc
Hospira inc

Packagers

Dosage forms

Form	Route	Strength
Solution	Intravenous
Tablet	Oral

Prices

Unit description	Cost	Unit
Talwin 30 mg/ml vial	14.78 USD	ml
Talwin 30 mg/ml ampul	4.86 USD	ml
Talwin 30 mg/ml	1.64 USD	ml
Talwin 50 mg Tablet	0.47 USD	tablet

Patents

Not Available

Properties

State

solid

Melting point

146.3 oC

Experimental Properties

Property	Value	Source
logP	3.7	PhysProp
pKa	8.88	Various sources

Predicted Properties

Property	Value	Source
water solubility	1.22e-01 g/l	ALOGPS
logP	4.44	ALOGPS
logP	3.89	ChemAxon Molconvert
logS	-3.37	ALOGPS
pKa		ChemAxon Molconvert
hydrogen acceptor count	2	ChemAxon Molconvert
hydrogen donor count	1	ChemAxon Molconvert
polar surface area	23.47	ChemAxon Molconvert
rotatable bond count	2	ChemAxon Molconvert
refractivity	89.80	ChemAxon Molconvert
polarizability	33.86	ChemAxon Molconvert

References

Synthesis Reference

Not Available

General Reference

Not Available

External Links

Resource	Link
KEGG Drug	D00498
KEGG Compound	C07421
PubChem Compound	441278
PubChem Substance	46506363
ChemSpider	390041
BindingDB	50001028
Therapeutic Targets Database	DAP000356
PharmGKB	PA450852
Drug Product Database	2241976
RxList	http://www.rxlist.com/cgi/generic/pentazocine.htm
Drugs.com	http://www.drugs.com/cdi/pentazocine.html
Wikipedia	http://en.wikipedia.org/wiki/Pentazocine

ATC Codes

N02AD01

AHFS Codes

28:08.12

PDB Entries

Not Available

FDA label

Not Available

MSDS

show (48.4 KB)

Interactions

Drug Interactions

Not Available

Food Interactions

Take without regard to meals. Avoid alcohol.

Targets
1. Mu-type opioid receptor Pharmacological action: yes Actions: antagonist Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Receptor for beta-endorphin Organism class: human UniProt ID: P35372 Gene: OPRM1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Levine JD, Gordon NC: Synergism between the analgesic actions of morphine and pentazocine. Pain. 1988 Jun;33(3):369-72. Pubmed Martin BR, Katzen JS, Woods JA, Tripathi HL, Harris LS, May EL: Stereoisomers of [3H]-N-allylnormetazocine bind to different sites in mouse brain. J Pharmacol Exp Ther. 1984 Dec;231(3):539-44. Pubmed Kamei J, Iwamoto Y, Misawa M, Nagase H, Kasuya Y: Effects of diabetes on the antinociceptive effect of (+/-)pentazocine in mice. Res Commun Chem Pathol Pharmacol. 1994 Apr;84(1):105-10. Pubmed Picker MJ, Benyas S, Horwitz JA, Thompson K, Mathewson C, Smith MA: Discriminative stimulus effects of butorphanol: influence of training dose on the substitution patterns produced by Mu, Kappa and Delta opioid agonists. J Pharmacol Exp Ther. 1996 Dec;279(3):1130-41. Pubmed Saha N, Datta H, Sharma PL: Effects of morphine, buprenorphine, pentazocine and nalorphine on acquisition and extinction of active avoidance responses in rats. Indian J Physiol Pharmacol. 1990 Jul;34(3):179-82. Pubmed 2. Kappa-type opioid receptor Pharmacological action: yes Actions: agonist Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Receptor for dynorphins. May play a role in arousal and regulation of autonomic and neuroendocrine functions Organism class: human UniProt ID: P41145 Gene: OPRK1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Chien CC, Pasternak GW: (-)-Pentazocine analgesia in mice: interactions with a sigma receptor system. Eur J Pharmacol. 1995 Dec 27;294(1):303-8. Pubmed 3. Sigma 1-type opioid receptor Pharmacological action: yes Actions: agonist Organism class: human UniProt ID: Q99720 Gene: OPRS1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Chien CC, Pasternak GW: (-)-Pentazocine analgesia in mice: interactions with a sigma receptor system. Eur J Pharmacol. 1995 Dec 27;294(1):303-8. Pubmed Colabufo NA, Contino M, Inglese C, Niso M, Perrone R, Roperto S, Roperto F: In vitro and ex vivo characterization of sigma-1 and sigma-2 receptors: agonists and antagonists in biological assays. Cent Nerv Syst Agents Med Chem. 2009 Sep;9(3):161-71. Pubmed Dun Y, Thangaraju M, Prasad P, Ganapathy V, Smith SB: Prevention of excitotoxicity in primary retinal ganglion cells by (+)-pentazocine, a sigma receptor-1 specific ligand. Invest Ophthalmol Vis Sci. 2007 Oct;48(10):4785-94. Pubmed Mamolo MG, Zampieri D, Zanette C, Florio C, Collina S, Urbano M, Azzolina O, Vio L: Substituted benzylaminoalkylindoles with preference for the sigma2 binding site. Eur J Med Chem. 2008 Oct;43(10):2073-81. Epub 2007 Sep 26. Pubmed Pal A, Hajipour AR, Fontanilla D, Ramachandran S, Chu UB, Mavlyutov T, Ruoho AE: Identification of regions of the sigma-1 receptor ligand binding site using a novel photoprobe. Mol Pharmacol. 2007 Oct;72(4):921-33. Epub 2007 Jul 10. Pubmed

Targets

1. Mu-type opioid receptor

Pharmacological action: yes
Actions: antagonist

Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Receptor for beta-endorphin

Organism class: human
UniProt ID: P35372 Link_out

Gene: OPRM1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Levine JD, Gordon NC: Synergism between the analgesic actions of morphine and pentazocine. Pain. 1988 Jun;33(3):369-72. Pubmed
Martin BR, Katzen JS, Woods JA, Tripathi HL, Harris LS, May EL: Stereoisomers of [3H]-N-allylnormetazocine bind to different sites in mouse brain. J Pharmacol Exp Ther. 1984 Dec;231(3):539-44. Pubmed
Kamei J, Iwamoto Y, Misawa M, Nagase H, Kasuya Y: Effects of diabetes on the antinociceptive effect of (+/-)pentazocine in mice. Res Commun Chem Pathol Pharmacol. 1994 Apr;84(1):105-10. Pubmed
Picker MJ, Benyas S, Horwitz JA, Thompson K, Mathewson C, Smith MA: Discriminative stimulus effects of butorphanol: influence of training dose on the substitution patterns produced by Mu, Kappa and Delta opioid agonists. J Pharmacol Exp Ther. 1996 Dec;279(3):1130-41. Pubmed
Saha N, Datta H, Sharma PL: Effects of morphine, buprenorphine, pentazocine and nalorphine on acquisition and extinction of active avoidance responses in rats. Indian J Physiol Pharmacol. 1990 Jul;34(3):179-82. Pubmed

2. Kappa-type opioid receptor

Pharmacological action: yes
Actions: agonist

Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Receptor for dynorphins. May play a role in arousal and regulation of autonomic and neuroendocrine functions

Organism class: human
UniProt ID: P41145 Link_out

Gene: OPRK1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Chien CC, Pasternak GW: (-)-Pentazocine analgesia in mice: interactions with a sigma receptor system. Eur J Pharmacol. 1995 Dec 27;294(1):303-8. Pubmed

3. Sigma 1-type opioid receptor

Pharmacological action: yes
Actions: agonist
Organism class: human
UniProt ID: Q99720 Link_out

Gene: OPRS1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Chien CC, Pasternak GW: (-)-Pentazocine analgesia in mice: interactions with a sigma receptor system. Eur J Pharmacol. 1995 Dec 27;294(1):303-8. Pubmed
Colabufo NA, Contino M, Inglese C, Niso M, Perrone R, Roperto S, Roperto F: In vitro and ex vivo characterization of sigma-1 and sigma-2 receptors: agonists and antagonists in biological assays. Cent Nerv Syst Agents Med Chem. 2009 Sep;9(3):161-71. Pubmed
Dun Y, Thangaraju M, Prasad P, Ganapathy V, Smith SB: Prevention of excitotoxicity in primary retinal ganglion cells by (+)-pentazocine, a sigma receptor-1 specific ligand. Invest Ophthalmol Vis Sci. 2007 Oct;48(10):4785-94. Pubmed
Mamolo MG, Zampieri D, Zanette C, Florio C, Collina S, Urbano M, Azzolina O, Vio L: Substituted benzylaminoalkylindoles with preference for the sigma2 binding site. Eur J Med Chem. 2008 Oct;43(10):2073-81. Epub 2007 Sep 26. Pubmed
Pal A, Hajipour AR, Fontanilla D, Ramachandran S, Chu UB, Mavlyutov T, Ruoho AE: Identification of regions of the sigma-1 receptor ligand binding site using a novel photoprobe. Mol Pharmacol. 2007 Oct;72(4):921-33. Epub 2007 Jul 10. Pubmed

Comments

Drug created on June 13, 2005 07:24 / Updated on November 10, 2010 13:41

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