Drugs online research references
J Pharmacol Exp Ther. 1988 Aug;246(2):493-9.
Inhibition of acid secretion in guinea pigs by tricyclic antidepressants: comparison with ranitidine and omeprazole.
Batzri S, Brugada O, Harmon JW, Rich NM.
Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
The antisecretory properties of imipramine on gastric secretion in guinea pig in comparison with other antisecretory agents was determined. In awake guinea pigs s.c. infusion of histamine (30 micrograms/kg/hr) increased acid and fluid secretion by 3- to 4-fold. When acid output peaked, a bolus administration of the tricyclic anti-depressant imipramine inhibited acid and fluid secretion. Imipramine and other agents, such as ranitidine and omeprazole, inhibited gastric secretion in a dose-dependent fashion. The most potent was the H2-antagonist ranitidine (IC50, 0.2-0.3 mumol/kg), followed by the gastric H-K-adenosine triphosphatase inhibitor, omeprazole (IC50, 0.5-0.6 mumol/kg). Imipramine (IC50 1-2 mumol/kg) was the least potent of the inhibitors. Both ranitidine and omeprazole could abolish acid secretion, but maximal inhibition with imipramine was 60% of initial. Promethazine (25 mumol/kg), an H1 antagonist, and atropine (12 mumol/kg), a muscarinic antagonist, inhibited gastric secretion by 40 to 50%. Imipramine and atropine also inhibited basal acid secretion. In dispersed gastric cells comparison between imipramine and omeprazole showed that imipramine was about 5-fold more potent than omeprazole in blocking histamine or dibutyryl cyclic AMP stimulation of aminopyrine accumulation. Imipramine probably acts as a protonophore by increasing the rate of proton-gradient dissipation rather than by interfering with the hydrogen-pump system because, in gastric membranes, imipramine was 20-fold less potent than omeprazole in inhibiting the gastric H-K-adenosine triphosphatase activity. These results suggest that imipramine administered s.c. in guinea pigs is a potent antisecretory drug. Its action may be due to a combination of anticholinergic and antihistamine H2 activities.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2841448&dopt=Abstract
Ann Otol Rhinol Laryngol. 1985 May-Jun;94(3):313-8.
Unusual effects of histamine antagonists on canine nasal blood vessels.
Ichimura K, Jackson RT.
This paper documents some of the lesser-known effects of antihistamines on nasal blood vessel smooth muscle. An in vitro muscle tension detecting technique was utilized. Three different H1 receptor antagonists (pyrilamine maleate, chlorpheniramine maleate, promethazine hydrochloride), and the H2 antagonist metiamide were used. Besides their basic antihistaminic effect, H1 antagonists (classical antihistamines) induced a contraction, enhanced norepinephrine- and epinephrine-induced contractions, and relaxed the sustained contraction induced by methoxamine hydrochloride or high concentrations of potassium. Although these effects were quite similar to those induced by histamine, the mechanism of each effect was apparently different. Metiamide did not produce these effects except for the relaxation of the sustained contraction. The actions of histamine antagonists seem to be much more complicated than expected.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2861783&dopt=Abstract
Pharmacol Biochem Behav. 1986 Apr;24(4):925-30.
The effect of antihistaminic drugs on pentazocine antinociception in the rat.
Yeh SY.
The antinociception produced by pentazocine, diphenhydramine, promethazine, chlorpheniramine, cyclizine and chlorcyclizine in the rat has been measured with a low-temperature (51.5 degrees C) hot-plate from 15 to 75 min following drug administration. The mean reaction times measured at 15 min and the area under the antinociception curves following administration of pentazocine (5 to 30 mg/kg) were linear. Diphenhydramine, chlorpheniramine, promethazine, cyclizine, and chlorcyclizine showed mild antinociceptive potency. The antinociception produced by SC pentazocine (5 and 10 mg/kg) was potentiated, rather than in a simple additive manner, by simultaneous IP administration of 20 mg/kg of diphenhydramine, promethazine, cyclizine, or chlorpheniramine, but not by chlorcyclizine. After concurrent administration of pentazocine and diphenhydramine, diphenhydramine did not alter pentazocine concentrations in the brain and plasma 15 to 75 min following drug administration, nor did pentazocine change diphenhydramine concentrations. Results of this study demonstrate that pentazocine antinociception can be potentiated by several antihistamines and that the potentiation was not due to a mutual effect on metabolism but rather through an as yet undefined mechanism.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2872685&dopt=Abstract
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