Pentamidin

Bezeichnung:Pentamidin

CAS-Nr100-33-4

Englisch Name:Pentamidine

CBNumberCB4476092

SummenformelC19H24N4O2

Molgewicht340.42

MOL-Datei100-33-4.mol

Synonyma

Pentamidin

Pentamidin physikalisch-chemischer Eigenschaften

Schmelzpunkt	186 °C (dec.)
Siedepunkt	476.22°C (rough estimate)
Dichte	1.1805 (rough estimate)
Brechungsindex	1.6620 (estimate)
storage temp.	Sealed in dry,Store in freezer, under -20°C
Löslichkeit	DMSO, Methanol (Sparingly)
Aggregatzustand	Solid
pka	pKa 11.4 (Uncertain)
Farbe	White to Off-White

Sicherheit

RIDADR	3249
HazardClass	6.1(b)
PackingGroup	III
Giftige Stoffe Daten	100-33-4(Hazardous Substances Data)

Gefahreninformationscode (GHS)

Pentamidine Chemische Eigenschaften,Einsatz,Produktion Methoden

Beschreibung
Pentamidine is an aromatic diamine that is effective against protozoal diseases, such as amoebic dysentery, malaria, trypanosomiasis, and leishmaniasis. In clinical studies, it has also been shown to be an effective prophylaxis against pneumocystis pneumonia.
Chemische Eigenschaften
Crystalline Solid
Originator
Nebupent,Fujisawa Healthcare Inc ,USA
Verwenden
Has been widely used as a drug to treat protozoal diseases, such as malaria, amoebic dysentery and trypanosomiasis. It has also been shown to be effective for both prophylaxis of pneumocystic carinii pneumonia (PCC).
Verwenden
antiprotozoal, inhibits nucleic acid & protein synthesis
Indications
Pentamidine (Pentam 300) binds to DNA and may inhibit kinetoplast DNA replication and function. It also may act by inhibiting dihydrofolate reductase and interfering with polyamine metabolism. An effect on organism respiration, especially at high doses, also may play a role.
Definition
ChEBI: Pentamidine is a diether consisting of pentane-1,5-diol in which both hydroxyl hydrogens have been replaced by 4-amidinophenyl groups. A trypanocidal drug that is used for treatment of cutaneous leishmaniasis and Chagas disease. It has a role as a trypanocidal drug, an antifungal agent, a NMDA receptor antagonist, an anti-inflammatory agent, a chemokine receptor 5 antagonist, an EC 2.3.1.48 (histone acetyltransferase) inhibitor, a calmodulin antagonist, a S100 calcium-binding protein B inhibitor and a xenobiotic. It is a carboxamidine, a diether and an aromatic ether. It is a conjugate base of a pentamidinium(2+).
Manufacturing Process
2.5 g of p,p'-dicyano-1,5-diphenoxy-pentane (obtained by the interaction of phydroxybenzonitrile and pentamethylene-dibromide in aqueous alkaline solution, melting point 114°C) are dissolved in 15 cc of nitrobenzene and 2.5 cc of absolute ethyl alcohol added. The solution is saturated with dry hydrochloric acid gas at 0°C and allowed to stand for 48 h. It is then diluted with dry ether and the precipitated 1,5-diphenoxypentane, 4,4'di(ethoxycarbonimidoyl) dihydrochlorid is filtered and washed with ether.
4 g of 1,5-diphenoxypentane, 4,4'-di(ethoxycarbonimidoyl) dihydrochloride are mixed with 30 cc. of 6 % ethyl alcoholic ammonia and heated in a closed vessel at 50°C for 5 h. The alcohol is removed and the residual 1,5diphenoxypentane, 4,4'-diamidino dihydrochloride is twice recrystallised fromdilute hydrochloric acid and finally purifled by dissolving in water and precipitating with acetone. Its melts at 236°C, dec.
Pentamidine isetionate salt may be produced by the reaction pentamidine base with isethionic acid.
Trademarks
Nebupent [as isethionate] (Fujisawa); Pentacarinat [as isethionate] (Rhone-Poulenc Rorer); Pentam 300 [as isethionate] (Fujisawa).
Therapeutic Function
Antiprotozoal
Antimicrobial activity
Pentamidine has broad activity in experimental models against P. falciparum, Toxoplasma gondii, Leishmania spp., Trypanosoma spp. and Babesia spp. It also has activity against Pn. jirovecii.
Acquired resistance
Relapse rates of 7–16% have been reported in the treatment of human African trypanosomiasis in West Africa. Patients usually respond to a subsequent course of treatment with melarsoprol. A membrane transporter is involved in crossresistance of arsenic-resistant T. brucei to diamidines, affecting diminazene and stilbamidine more than pentamidine.
Pharmazeutische Anwendungen
A synthetic diamidine, available as the isethionate (2-hydroxymethane sulfonate) salt for parenteral use. It is also administered by instillation of a nebulized solution directly into the lungs.
Mechanism of action
Pentamidine is not well absorbed from the intestinal tract after oral administration and generally is given by intramuscular injection. The drug binds to tissues, particularly the kidney, and is slowly excreted, mostly as the unmodified drug. It does not enter the central nervous system (CNS). Its sequestration in tissues accounts for its prophylactic use in trypanosomiasis.
Pharmakokinetik
Oral absorption: Negligible
C_max 4 mg/kg intramuscular: c. 0.5 mg/L after 1 h
Plasma half-life: c. 6.5 h
Volume of distribution: 3 L/kg
Plasma protein binding: c. 70%
Pentamidine is rapidly and extensively metabolized by rat liver, and high concentrations are retained in renal and hepatic tissue for up to 6 months after administration. In humans distribution is mainly in the liver, kidney, adrenal glands and spleen, with lower accumulation in the lung. This tissue retention is the basis for its prophylactic use. Although transport across the blood–brain barrier has been demonstrated in experimental models, it is probably unable to cross the blood–brain barrier in sufficient quantity to be trypanocidal: <1% of the plasma concentration has been measured in the CSF of sleeping sickness patients. About 15–20% of the dose is excreted in the urine but because of retention in tissues there is an extremely long terminal half-life (>12 days).
Clinical Use
Pentamidine is active against Pneumocystis carinii, trypanosomes, and leishmaniasis unresponsive to pentavalent antimonials. It is an alternative agent for the treatment of P. carinii pneumonia. Although it is more toxic than trimethoprim–sulfamethoxazole, it has been widely used in patients with acquired immunodeficiency syndrome (AIDS), in whom P. carinii infection is common.
Pentamidine is an alternative drug for visceral leishmaniasis, especially when sodium stibogluconate has failed or is contraindicated. Pentamidine is also a reserve agent for the treatment of trypanosomiasis before the CNS is invaded. This characteristic largely restricts its use to Gambian trypanosomiasis.
Clinical Use
Human African trypanosomiasis (early stages before CNS involvement) Prophylaxis and therapy of Pn. jirovecii pneumonia
Visceral leishmaniasis unresponsive to pentavalent antimonials and cutaneous leishmaniasis caused by L. guyanensis
There is limited evidence for its use in the treatment of babesiosis.
Nebenwirkungen
Side effects range from local irritation and sterile abscess at the site of injection to transient effects (vomiting, abdominal discomfort) and serious systemic effects (hypotension, effects on the heart, hypoglycemia and hyperglycemia, leukopenia, thrombocytopenia). In a study of the treatment of South American cutaneous leishmaniasis, 17% of patients prematurely terminated treatment due to toxicity and another 30% reported side effects.
Nebenwirkungen
Adverse reactions occur frequently. Rapid drug infusion may produce tachycardia, vomiting, shortness of breath, headache, and a fall in blood pressure. Changes in blood sugar (hypoglycemia or hyperglycemia) necessitate caution in its use, particularly in patients with diabetes mellitus. Renal function should be monitored and blood counts checked for dyscrasias.
Synthese
Pentamidine, 4-4??-(pentamethylendioxy)dibenzamidine (37.4.2), is made by reacting 4-hydroxybenzonitrile with 1,5-dibromopentane in the presence of sodium hydroxide to make 1,5-bis-(4-cyanophenoxy)pentane (37.4.1). Subsequent reaction of this with an ethanol solution of hydrogen chloride with the intermediate formation of an iminoester, and then with an ethanol solution of ammonia gives the desired pentamidine.

Pentamidin Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

100-33-4, Pentamidine Verwandte Suche:

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