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Target Concepts:
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Query: UNIPROT:P01185 (
vasopressin
)
23,126
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Preliminary studies determined that, unlike other purported alpha-2 adrenoceptor agonists, 2,6-dimethyl clonidine (2,6-
DMC
) increased urine flow rate independent of
vasopressin
. We therefore compared the dose-response curves of three alpha-2 adrenoceptor agonists, clonidine, UK 14,304 and 2,6-
DMC
. Unilaterally nephrectomized Sprague-Dawley rats were anesthetized and the left kidney was exposed and the ureter cannulated. A 31-gauge needle was advanced into the renal artery to permit direct intrarenal infusion of the study drugs. All three agonists produced a dose-related increase in urine flow rate and sodium excretion. A clear opposite rank order of potency was observed when the urine flow rate was analyzed as free water and osmolar clearance. For free water clearance, clonidine much greater than UK 14,304 much greater than 2,6-
DMC
, with 2,6-
DMC
producing little change. The effect on osmolar clearance was opposite with 2,6-
DMC
much greater than clonidine = UK 14,304. The V2 antagonist [1-(beta-mercapto-beta,beta-pentamethylene-proprionic acid), 2-d-isoleucine,4-isoleucine]
arginine-vasopressin
blocked the effects of clonidine but not 2,6-
DMC
. In a water-loaded rat model, 2,6-
DMC
but not clonidine increased the delivery of filtrate out of the proximal segments of the nephron. These results are consistent with the postulate that lower doses of 2,6-
DMC
increase solute excretion independent of
vasopressin
, possibly in proximal segments of the nephron. Clonidine on the other hand increases free water clearance and this effect is mediated through an interaction with the renal actions of
vasopressin
. Whether these disparate effects represent two distinct receptors or two sites of alpha-2 adrenoceptors in the kidney is not known.
...
PMID:Opposite rank order of potency for alpha-2 adrenoceptor agonists on water and solute excretion in the rat: two sites and/or receptors? 135 Oct 96
Carbamazepine (CBZ)-induced water intoxication occasionally limits its usefulness in refractory seizures and trigeminal neuralgia. Fluid restriction, CBZ dose reduction, or concomitant phenytoin therapy may be impractical or ineffective. Demeclocycline (7-chloro-6 demethyl tetracycline) (
DMC
) corrected the CBZ-induced water intoxication in a 51-year-old man with refractory complex partial seizures and a normal
antidiuretic hormone
(
ADH
) level.
DMC
inhibits
ADH
-sensitive adenylate cyclase activity in the renal collecting duct and may be useful in correcting the
ADH
-like or renal antidiuretic effect of CBZ.
...
PMID:Perspective on carbamazepine-induced water intoxication: reversal by demeclocycline. 309 19