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Titolo:
PHARMACOKINETIC ALPHA(1)-ADRENOCEPTOR ANTAGONISTIC PROPERTIES OF 2 CYANINE-TYPE INHIBITORS OF EXTRANEURONAL MONOAMINE TRANSPORT
Autore:
RUSS H; FRIEDGEN B; KONIGS B; SCHUMACHER C; GRAEFE KH; SCHOMIG E;
Indirizzi:
UNIV REGENSBURG,NEUROL & PSYCHIAT KLIN,UNIV STR 84 D-93042 REGENSBURGGERMANY UNIV WURZBURG,INST PHARMAKOL & TOXIKOL D-97078 WURZBURG GERMANY RHEIN WESTFAL TH AACHEN,MED KLIN D-52057 AACHEN GERMANY UNIV HEIDELBERG,INST PHARMAKOL D-69120 HEIDELBERG GERMANY
Titolo Testata:
Naunyn-Schmiedeberg's archives of pharmacology
fascicolo: 3, volume: 354, anno: 1996,
pagine: 268 - 274
SICI:
0028-1298(1996)354:3<268:PAAPO2>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
ALPHA-ADRENOCEPTOR SUBTYPES; HIGH-AFFINITY; NORADRENALINE TRANSPORT; THORACIC AORTA; BLOOD-VESSELS; ALPHA-1-ADRENOCEPTORS; RABBIT; RATS; )I-125>-HEAT; RADIOLIGAND;
Keywords:
ALPHA-1-ADRENOCEPTOR; DECYNIUM22; DISPROCYNIUM24; EXTRANEURONAL MONOAMINE TRANSPORTER; PHARMACOKINETICS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
35
Recensione:
Indirizzi per estratti:
Citazione:
H. Russ et al., "PHARMACOKINETIC ALPHA(1)-ADRENOCEPTOR ANTAGONISTIC PROPERTIES OF 2 CYANINE-TYPE INHIBITORS OF EXTRANEURONAL MONOAMINE TRANSPORT", Naunyn-Schmiedeberg's archives of pharmacology, 354(3), 1996, pp. 268-274

Abstract

1,1'-Diethyl-2,2'-cyanine (decynium22) and 1,1'-diisopropyl-2,4'-cyanine (disprocynium24) are highly potent inhibitors of the extraneuronalmonoamine transporter. When given as i.v. bolus injections (4 mu mol kg(-1)) to anaesthetized rabbits, both drugs elicited a transient fallin blood pressure without altering heart rate. The observed maximum fall in diastolic blood pressure was 59% after decynium22 and 43% afterdisprocynium24 administration. The pharmacokinetics of decynium22 anddisprocynium24 were similar; they were characterized by short half-lives for elimination (8.2 and 4.5 min, respectively) and very high plasma clearances (173 and 180 ml kg(-1) min(-1), respectively). The mechanism underlying the blood pressure-lowering effect of decynium22 was explored in the isolated incubated rabbit aorta. Decynium22 antagonizedthe noradrenaline-induced contraction; the pA(2) for this interactionwas 7.6, and the slope of the corresponding Schild plot was unity. Zna membrane preparation from rat myocardium, decynium22 as well as disprocynium24 inhibited the specific binding of -hydroxy-3-iodophenyl)-ethylaminomethyl]-tetralone (I-125-HEAT), a selective ligand to alpha(1)-adrenoceptors. The K-i's were 5.3 and 240 nmol l(-1) for decynium22 and disprocynium24, respectively. The type of binding inhibition by decynium22 was competitive. It is concluded that the two inhibitors of extraneuronal monoamine transport decynium22 and disprocynium24 lower blood pressure by blocking alpha(1)-adrenoceptors. A comparison of their potencies in blocking extraneuronal monoamine transport and alpha(1)-adrenoceptors clearly indicates that disprocynium24 is more suitable for studies designed to determine the role of extraneuronal monoamine transport in vivo. Considering its very fast elimination kinetics, disprocynium24 must be administered by constant rate-infusions in order to avoid large fluctuations of plasma levels.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/07/20 alle ore 23:58:30