Papaverine

Papaverine

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Systematic (IUPAC) name
1-(3,4-dimethoxybenzyl)-6,7-dimethoxyisoquinoline
Clinical data
Pregnancy category	USA: C
Routes of administration	Oral, intravenous, intramuscular, rectal, intracavernosal
Pharmacokinetic data
Bioavailability	80%
Protein binding	~90%
Metabolism	Hepatic
Biological half-life	1.5–2 hours
Excretion	Renal
Identifiers
CAS Number	58-74-2 61-25-6 (hydrochloride)
ATC code	A03AD01 (WHO) G04BE02
PubChem	CID 4680
DrugBank	APRD00628
Chemical data
Formula	C20H21NO4
Molar mass	339.385 g/mol[[]]
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Papaverine (pronounced /pəˈpævəriːn/) is an opium alkaloid used primarily in the treatment of visceral spasm, vasospasm (especially those involving the heart and the brain), and occasionally in the treatment of erectile dysfunction. While it is found in the opium poppy, papaverine differs in both structure and pharmacological action from the analgesic (morphine-related) opium alkaloids (opioids).

Uses

Papaverine is approved to treat spasms of the gastrointestinal tract, bile ducts and ureter and for use as a cerebral and coronary vasodilator in subarachnoid hemorrhage (combined with balloon angioplasty) and coronary artery bypass surgery. Papaverine may also be used as a smooth muscle relaxant in microsurgery where it is applied directly to blood vessels.

It is also commonly used in cryopreservation of blood vessels along with the other glycosaminoglycans and protein suspensions. Functions as a vasodilator during cryopreservation when used in conjunction with verapamil, phentolamine, nifedipine, tolazoline or nitroprusside.

Papaverine is also being investigated as a topical growth factor in tissue expansion with some success.

Papaverine is also present in combinations of opium alkaloid salts such as Omnopon, Pantopon, Papaveretum, and others along with morphine, codeine, and in some cases noscapine and others in a percentage similar to that in opium or modified for a given application.

Mechanism

The in vivo mechanism of action is not entirely clear, but an inhibition of the enzyme phosphodiesterase causing elevation of cyclic AMP levels is significant. It may also alter mitochondrial respiration.

Papaverine has also been demonstrated to be a selective phosphodiesterase inhibitor for the PDE_10A subtype found mainly in the striatum of the brain. When administered chronically to mice it produced motor and cognitive deficits and increased anxiety, but conversely may produce an antipsychotic effect., even though not all studies support this view .

Side effects

Frequent side effects of papaverine treatment include polymorphic ventricular tachycardia, constipation, interference with sulphobromophthalein retention test (used to determine hepatic function), increased transaminase levels, increased alkaline phosphatase levels, somnolence, and vertigo.

Rare side effects include flushing of the face, hyperhidrosis (excessive sweating), cutaneous eruption, arterial hypotension, tachycardia, loss of appetite, jaundice, eosinophilia, thrombopenia, mixed hepatitis, headache, allergic reaction, chronic active hepatitis, and paradoxical aggravation of cerebral vasospasm.

Formulations and trade names

Papaverine is available as a conjugate of hydrochloride, codecarboxylate, adenylate, and teprosylate. It was also once available as a salt of hydrobromide, camsylate, cromesilate, nicotinate, and phenylglycolate. The hydrochloride salt is available for intramuscular, intravenous, rectal and oral administration. The teprosylate is available in intravenous, intramuscular, and orally administered formulations. The codecarboxylate is available in oral form, only, as is the adenylate.

The codecarboxylate is sold under the name Albatran, the adenylate as Dicertan, and the hydrochloride salt is sold variously as Artegodan (Germany), Cardioverina (countries outside Europe and the United States), Dispamil (countries outside Europe and the United States), Opdensit (Germany), Panergon (Germany), Paverina Houde (Italy, Belgium), Pavacap (United States), Pavadyl (United States), Papaverin-Hamelin (Germany), Paveron (Germany), Spasmo-Nit (Germany), Cardiospan, Papaversan, Cepaverin, Cerespan, Drapavel, Forpaven, Papalease, Pavatest, Paverolan, Therapav (France), Vasospan, Cerebid, Delapav, Dilaves, Durapav, Dynovas, Optenyl, Pameion, Papacon, Pavabid, Pavacen, Pavakey, Pavased, Pavnell, Alapav, Myobid, Vasal, Pamelon, Pavadel, Pavagen, Ro-Papav, Vaso-Pav, Papanerin-hcl, Qua bid, Papital T.R., Paptial T.R., Pap-Kaps-150.. In Hungary papaverine and homatropine-methylbromide are used in mild drugs that help "flush" the bile (e.g. Neo-Bilagit).

References

1. ^{a b c} "SID 544606 — PubChem Substance Summary". 
2. ^a "Papaverine Material Safety Data Sheet". Retrieved 25 September 2005. 
3. ^{a b c d e f g h} Unknown (2000). "PAPAVERINE". Molécule(s) de base: PAPAVERINE. Biam. Retrieved 25 September 2005.  (French)
4. ^a Unknown (2004). "Who should not take papaverine?". papaverine Consumer Drug Information. Cerner Multum, Inc. Retrieved 26 September 2005. 
5. ^{a b c} Unknown (1999). "PAPAVERINE CHLORHYDRATE". Molécule(s) de base: PAPAVERINE. Biam. Retrieved 25 September 2005.  (French)
6. ^a Liu JK, Couldwell WT (2005). "Intra-arterial papaverine infusions for the treatment of cerebral vasospasm induced by aneurysmal subarachnoid hemorrhage". Neurocrit Care. 2 (2): 124–32. doi:10.1385/NCC:2:2:124. PMID 16159054. 
7. ^a
8. ^a "SID 149219 — PubChem Substance Summary". 
9. ^a
10. ^a "Molécule de base: PAPAVERINE". Retrieved 26 September 2005.  Biam.
11. ^a Unknown (1999). "PAPAVERINE TEPROSILATE". Molécule(s) de base: PAPAVERINE. Biam. Retrieved 26 September 2005.  (French)
12. ^a Unknown (1998). "PAPAVERINE CODECARBOXYLATE". Molécule(s) de base: PAPAVERINE. Biam. Retrieved 26 September 2005.  (French)
13. ^a Unknown (1998). "PAPAVERINE ADENYLATE". Molécule(s) de base: PAPAVERINE. Biam. Retrieved 26 September 2005.  (French)
14. ^a "SID 660773 — PubChem Substance Summary". 
15. ^a "SID 660767 — PubChem Substance Summary". 
16. ^a "THERAPAV (PRODUIT PUR) - Détail". Retrieved 26 September 2005.  CSST - Service du répertoire toxicologique. (French)
17. ^a "SID 660767 — PubChem Substance Summary — Depositor-Supplied Synonyms: All". 

ca:Papaverina uk:Папаверин