The influence of debrisoquin on the accumulation and metabolism of biogenic amines by the human platelet, in vivo and in vitro

Solomon, Harvey M.; Ashley, Constance J.; Spirt, Nena; Abrams, William B.

doi:10.1002/cpt1969102229

Cited by 36 publications

(8 citation statements)

References 5 publications

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“…Estimations of D from platelet lysates confirms this to be the case (Leninard, Silas, Smith & Tucker, 1977b). The importance of these data may lie in the similarity between platelet and neuronal uptake of D (Solomon, Ashley, Spirit & Abrams, 1969). Platelet, rather than plasma D concentration, may best reflect the intraneuronal pool and hypotensive effect of this drug.…”

Section: Discussionmentioning

confidence: 99%

The disposition of debrisoquine in hypertensive patients.

Silas¹,

Lennard²,

Tucker³

et al. 1978

Brit J Clinical Pharma

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I The urinary recovery and plasma concentration of debrisoquine (D) and its metabolite 4-hydroxydebrisoquine (HD) has been studied following single and multiple oral administration of debrisoquine hemisulphate to 15 hypertensive in-patients and four normal volunteers. The distribution of D in the blood was studied after a single dose to one volunteer. The greatest concentration of the drug was in the platelet rich fraction from which it was eliminated slowly. The elimination half-lives in plasma and platelet rich plasma were 17.5 h and 56 h respectively. 7 On early multiple dosing the hypotensive response was related to high plasma D concentrations.

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Section: Discussionmentioning

confidence: 99%

The disposition of debrisoquine in hypertensive patients.

Silas¹,

Lennard²,

Tucker³

et al. 1978

Brit J Clinical Pharma

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“…This observation would suggest that the up take of the former three blockers is completely energy dependant while the uptake of debriso quin is only partly so. O'Brien & Boullin (17) obtained 97.5% inhibition of uptake of debrisoquin (1 x 10-6 M) at 4 C by mammalian platelets which serve as model for the up take and binding system in noradrenergic nerve endings in the periphery (13). A higher concentration of debrisoquin (8.4 ,11, 10-` M) was used herein.…”

Section: Discussionmentioning

confidence: 99%

“…A possibility may be that although these three neuron blockers are taken up by the adrenergic neuron through a mechanism distinct from the one concerned with the uptake of NA, a suggestion already made for bretylium (19,22), intraneuronally accumulated NA resulting from exposure to high concentrations of NA may not allow effective intraneuronal concentrations of the three neuron blockers to be built up. Debrisoquin, bretylium and xylocholine are known to possess MAO in hibitory action (13,23,24). Effective reduction of the intraneuronal concentration of bretylium during exposure to tyramine has been explained as due to a competition between tyramine and bretylium at the enzyme MAO and a number of sites besides the enzyme MAO (23).…”

Section: Discussionmentioning

confidence: 99%

“…Guanethidine utilises this NA uptake me chanism for transport across the membrane of neurons (10,11) and of human platelets (12) which can serve as convenient model for the neuron (13). Support for this common transport mechanism for NA and guanethidine is derived from observations of the ability of NA to block the uptake of guanethidine, and the failure of uptake of guanethidine in sodium-deficient medium and under conditions of reduced energy supply as at low temp.…”

Section: Bretyliunmentioning

confidence: 99%

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Some Factors Affecting the Neuron Blocking Action of Guanethidine, Xylocholine, Bretylium and Debrisoquin

Prasad¹,

Shah²,

Gulati³

1973

Jpn.J.Pharmacol

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The uptake of guanethidine (3.3×10^-5 M), debrisoquin (8.4×10^-4 M), The uptake of noradrenaline (NA) by the adrenergic neuron is energy dependent (1, 2, 3) and sodium dependent (4,5,6, 7,8,9). Guanethidine utilises this NA uptake me chanism for transport across the membrane of neurons (10, 11) and of human platelets (12) which can serve as convenient model for the neuron (13). Support for this common transport mechanism for NA and guanethidine is derived from observations of the ability of NA to block the uptake of guanethidine, and the failure of uptake of guanethidine in sodium-deficient medium and under conditions of reduced energy supply as at low temp.(12). Gulati and Jaykar (14) showed that in the Finkleman preparation (15), the neuron blocking action of guanethidine was prevented by NA, sodium-deprivation and at low temp. and concluded that guanethidine shares the uptake mechanism for NA. Since the neuron blocking action of a neuron blocker is consequential upon the uptake by the neuron, the prevention of neuron block by various procedures and drugs affecting uptake of NA should provide information about the uptake of a neuron blocker. Thus the present cotn munication is concerned with the investigation of the influence of NA, low temp. and so dium-deprivation in modifying the adrenergic neuron blocking action on Hukovic pre paration (16) Of guanethidine, xylocholine, bretylitun and debrisoquin. In addition the mechanisms ol' the utitake Of these neuron bloekers into the adrenergic neurons are dis cussed.

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“…Thus, 5HT is localized in platelet granules along with ATP, and granular uptake and storage are reserpine sensitive, while the platelet membrane amine pump is Na+-dependent and ouabain-sensitive (27,(96)(97)(98)(99)(100). The major feature of the platelet system is its specificity for 5HT storage, illustrating again the ultimate specificity of the storage sys tem.…”

Section: Amine Transport and Storage In Dopamine Neurones And In Platmentioning

confidence: 93%

Transport and Storage of Biogenic Amines

Shore¹

1972

Annu. Rev. Pharmacol.

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The remarkable evolution of knowledge of the metabolism, transport, and storage of biogenic amines has come about to a large extent because of studies with drugs that interact with these processes. There are few better examples of the contribution of pharmacologic research to basic biology.Various aspects of biogenic amines and adrenergic mechanisms have been reviewed from time to time, and several excellent reviews may be found in previous issues of Annual Review of Pharmacology as well as other sources (1-8). The interested reader is referred to them.The present review will restrict itself generally to aspects of biogenic amine transport and storage in nervous tissue and with the interactions of selected drugs with these mechanisms. The discussion will address itself only to the biogenic monoamines, that is, the catecholamines and 5-hydroxy tryptamine (SHT). It will focus mostly on transport and storage of norepi nephrine at the adrenergic neurone, as it appears that this system serves generally as a model of the mechanisms involved in transport and storage of the other monoamines, although, to be sure, differences arise. Amine biosyn thesis and metabolism will not be touched upon except as pertinent to ques tions of transport and storage. As will be apparent to the reader, no attempt has been made to present a complete review of the vast literature on this subject.Two distinctly separate but linked systems exist at the level of mono amine neurones: an intraneuronal amine concentrating-storage mechanism associated with amine granules, and a neurone membrane amine pump. UPTAKE AND STORAGE BY AMINE GRANULESAlthough norepinephrine (NE) is found throughout the adrenergic neu rone, studies, mainly of peripheral adrenergic neurones, have revealed that this amine is present in highest concentration in the nerve terminal, with lesser amounts in the more proximal portion of the axon and in the cell body. The histochemical , fluorescence technique, which allows the visualiza tion of NE stores as well as other monoamines, reveals the presence of a filamentous network studded with enlargements or varicosities where NE is especially concentrated (see, for example, references 9,10). These varicosi ties seem to be groupings of the amine storage granules or vesicles as seen 209 Annu. Rev. Pharmacol. 1972.12:209-226. Downloaded from www.annualreviews.org Access provided by Columbia University on 02/05/15. For personal use only.Quick links to online content Further ANNUAL REVIEWS

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The influence of debrisoquin on the accumulation and metabolism of biogenic amines by the human platelet, in vivo and in vitro

Cited by 36 publications

References 5 publications

The disposition of debrisoquine in hypertensive patients.

The disposition of debrisoquine in hypertensive patients.

Some Factors Affecting the Neuron Blocking Action of Guanethidine, Xylocholine, Bretylium and Debrisoquin

Transport and Storage of Biogenic Amines

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