Drugs online research references
C R Acad Sci Hebd Seances Acad Sci D. 1976 Jul 19;283(3):283-6.
[Non-saturable cooperative binding of tolbutamide to rat endocrine pancreas. Criteria of specificity]
[Article in French]
Alric R, Manteghetti M, Puech R, Lignon F, Loubatieres A.
The binding of 3H-tolbutamide to isolated islets, which shows a cooperative non-saturable pattern up to about 5 X 10(-5) M, was confirmed. Binding to exocrine pancreatic tissue shows much less cooperativity. Among congeners of tolbutamide, unlabelled carbutamide and chlorpropamide in isodynamic concentrations, as well as diazoxide in an exactly antagonistic amount, behave like tolbutamide 5 X 10(-5) M itselt by cancelling cooperativity when added to the labelled drug. Glipizide and glibenclamide do not.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=825276&dopt=Abstract
J Auton Pharmacol. 1999 Dec;19(6):347-52.
Modification of cardiovascular responses to spinal GABA(B) receptor stimulation by cAMP and by K(ATP) channel blockade in anaesthetized rats.
Koh HC, Shin IC, Ha JH, Paik DJ, Kang JS, Lee CH.
Department of Pharmacology, College of Medicine, Hanyang University, Seoul, South Korea.
1. Intrathecal (i.t.) injection of baclofen (30, 60 and 100 nmol), a GABA(B) receptor agonist, produced a dose-dependent decrease in blood pressure (BP) and heart rate (HR). 2. Pretreatment with 5-aminovaleric acid (50 nmol), a GABA(B) receptor antagonist, blocked the depressor and bradycardic effects of baclofen (100 nmol). 3. Pretreatment with 8-bromo-cAMP (10 nmol), a cAMP analogue, attenuated the depressor and bradycardic effects of baclofen (100 nmol), but not with 8-bromo-cGMP (10 nmol), a cGMP analogue. 4. In addition, pretreatment with glipizide (20 nmol), an ATP-sensitive K+ channel (K(ATP)) blocker, attenuated the depressor and bradycardic effects of baclofen (100 nmol). These results suggest that GABA(B) receptors in the spinal cord have an inhibitory role in the central cardiovascular regulation and that these depressive and bradycardic actions are modified by cAMP and by K(ATP) channel blockade.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10961740&dopt=Abstract
Diabete Metab. 1975 Mar;1:13-21.
[Experimental study of glipizide. A comparison with other hypoglycemic sulfonamides (author's transl)]
[Article in French]
Loubatieres AL, Loubatieres-Mariani MM, Alric R, Ribes G, Sorial G, Tarasco A.
Glipizide is a new hypoglycaemic sulphonylurea. In this work we have studied experimentally the hypoglycaemic activity of this drug, its insulin secretory effect and its action on the development of the islets of Langerhans. Studies in the dog: In the normal conscious dog the hypoglycaemic effect of the drug was studied when increasing doses (0,03 mg/kg, 0,05 mg/kg, 0,07 mg/kg and 0,09 mg/kg) were injected intravenously. The hypoglycaemic effect of the drug occurred rapidly, reaching a maximum in about 30 minutes. The relative potency of glipizide was determined in comparison with tolbutamide. Under our experimental conditions, glipizide proved to be on average 99 times more active than tolbutamide when the doses were evaruated by weight; when the doses were expressed in moles it was 163 times more active. Plasma insulin levels manifested an increase at the first minute. This rose rapidly to a maximum at 5 to 15 minutes after the injection. Following this, insulinemia decreased and the values recorded at 60 minutes were about the same as the starting values. There is a linear relation between the logarithm of the dose and the area under the insulin curve measured for the first sixty minutes. After oral administration to the normal dog, glipizide (081 mg/kg and 1mg/kg) provoked a hypoglycemia manifested after a 30 to 60 minutes latent period. With the dose of 1 mg/kg the maximal effect on blood glucose level was reached between 1,30 and 3 hours, depending on the animal. Plasma insulin levels also increased after a latent period which varied from one animal to another. The dogs presenting the earliest increase in insulinemia were those in which glycemia drops most rapidly. Comparison with other sulfonamides (glibenclamide, glisoxepide and tolbutamide) showed that the hypoglycemic action of glipzide was very similar to that of glisoxepide and that it occurred much earlier than with glibenclamide. The insulin secretory effect of glipizide also occurred much earlier than that of glibenclamide, manifesting itself as early as that of glisoxepide and tolbutamide.Studies on the isolated rat pancreas: On the isolated rat pancreas perfused with Krebs-Ringer solution containing glucose (1,5 g/l), glipizide (10 mug/I) considerably increased the amount of secreted insulin. The stimulation of insulin secretion occurred rapidly and persisted powerfully during the entire duration of the infusion. It faded out progressively after stopping the infusion and the secretion remained higher than the control secretion during the following 45 minutes of the experiment. A concentration as low as 0,5 mug/I provoked a distinct increase of insulin secretion. Studies on the development of the islets of langerhans in the mouse: The prolonged administration of glipizide (100 mg/kg daily for 35 days) increased the "insular index", which is directly proportional to the islet weight, by 27%. Therefore this product possesses betacytotrophic activity...
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=825397&dopt=Abstract
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