A hypotensive activity

Some pyrazino[2,3-pyridazine derivatives show a preventive effect against cucumber powdery mildew. Unfortunately, none show a curative effect <89MI 719-01). l-Hydrazinopyridazine[4,5- ]qui-noxaline (103) shows an antihypertensive activity in spontaneously hypertensive rats and a hypotensive activity in normotensive anaesthetized rats <84JHC1271>. Some pyridazinoquinoxalines (104) are used as food additives and growth accelerators for pigs <80FRP2487352>. 

Try>bradykinin (N -i-tyroslne-bradykinin) is an N-terminally extended analogue of bradykiiiin and a (Bj) BRADYKININ RECEPTOR AGONIST. It is a HYPOTENSIVE active on a range of vascular and extravascular smooth muscle. It is used as a pharmacological tool. 

The 6-methoxybenzoxazolinone (25) isolated from S. dulcis showed a hypotensive activity [54]. 

OooQ>ound XTV, active at 1 mg/kg, i.v. in rabbits, is rex>orted to display a hypotensive activity similar to reserpine.22 The decahydro-isoquinoline derivative, XV, was also reported to have reserpine-like activity.23... 

Similarly, hypotensive activity is found in other analogues of hydralazine, including the very active endralazine (461) (79AF1835, 79AF1843), a pyrido[4,3-c]pyridazine. 

The association of a specific pharmacologic activity with certain functionality was remarked on earlier. The guanidino group, for example, often yields compounds that show hypotensive activity because of peripheral sympathetic blockade (see, for example, bethanidine). Attachment of a piperidine group to the side chain proves compatible with retention of this activity. 

Essential hypertension, whose prevalence is increased nearly two-fold in the diabetic population, may be another source of free-radical activity. The vascular lesions of hypertension can be produced by free-radical reactions (Selwign, 1983). In the recent Kuopio Ischaemic Heart Risk Factor Study in Finnish men, a marked elevation of blood pressure was associated with low levels of both plasma ascorbate and serum selenium (Salonen etal., 1988). A few studies report a hypotensive effect of supplementary ascorbate in patients with hypertension, but the actual changes in both systolic and diastolic pressure after ascorbate were not statistically significant in comparison with placebo (Trout, 1991). 

It is thus of note that a rather simple aminoquinoline shows hypotensive activity. 

During the course of a short and efficient total synthesis of (-) -dendrobine (3-76), an alkaloid which exhibits antipyretic and hypotensive activities [37], a new domino radical sequence has been exploited by Cassayre and Zard which involves the cycli-... 

Another potent peripheral vasodilator with hypotensive activity is minoxidil (U-10,858, XXXI). The drug was developed at the Upjohn Corporation, apparently as a follow-up of a previous clinical candidate, diallylmelamine -N-oxide (U-20,388, XXXII). The amine precursor, diallylmelamine (U-7720, XXXIII), is active in rats and dogs but not in man because the active... 

Welcome [67,68]. Bethanidine was initially patented as a hypotensive agent but was found to have antifibrillatory activity [69]. Attempts to limit the hypotensive effects of bethanidine led to meobentine. At a concentration of 44 fxM, bethanidine has minimal effects on APDioo in propranolol-treated and untreated canine Purkinje fibres (-1-2% and —5%, respectively) [70,71], At 350 //M in untreated fibres, bethanidine increased APDioo t>y about 6%. In contrast, meobentine, which has less sympatholytic activity, increased APDioo t>y 12% at 37 //M in untreated fibres during the same study. Both compounds showed modest decreases of V ax at the stated concentrations. The Class I activity and the sympatholytic activity (for bethanidine) may act to decrease the apparent Class III effects of the two compounds (see below). 

A Hungarian research group reported on the hypotensive activity of 3-(pyrazol-l-yl)pyridazines of type (72) in rats [253-256]. The activity of these compounds (in which both of the hydrazino nitrogen atoms are incorporated into a five-membered aromatic ring system) has been found to be mediated by inhibition of prostaglandin-catabolizing enzymes. 

It does not have a substantial effect on nonvascular smooth musculature or cardiac tissues. Homeostatic circulatory reflexes remain natural, and the resulting hypotension activates cardiovascular reflexes, which are expressed as an increase of heart work, power, and volume of cardiac output. Therefore, it is most effectively used in combination with )3-blockers. 

Noradrenaline is also sometimes added to local anaesthetics, again because of its vasoconstrictive properties. A prominent activity of this catecholamine is its ability to raise blood pressure. It is therefore used to restore blood pressure in acute hypotensive states. 

A number of theories have been put forward to account for the hypotensive action of a-methyldopa. Current evidence suggests that for a-methyldopa to be an antihypertensive agent, it must be converted to a-methyl-norepinephrine however, its site of action appears to be in the brain rather than in the periphery. Systemically administered a-methyldopa rapidly enters the brain, where it accumulates in noradrenergic nerves, is converted to a-methylnorepinephrine, and is released. Released a-methylnorepinephrine activates CNS a-adrenoceptors whose function is to decrease sympathetic outflow. Why a-methylnorepinephrine decreases sympathetic outflow more effectively than does the naturally occurring transmitter is not entirely clear. 

Hypotensive activity. Fruit juice, administered by intravenous infusion to dogs at a dose of 10 mL/minute for 30 minutes, was active Water extract of the fresh leaf and stem, administered intravenously to dogs at a dose of 0.1 mL/kg, was active " . Hypothermic activity. Ethanol (50%) extract of the leaf, administered intraperi-toneally to mice at a dose of 0.375 mg/kg, was inactive . 

Hypotensive activity. Essential oil, administered intravenously to dogs at a dose of 3 p,L/kg, was active. The ethanol (70%) extract, administered intravenously to dogs at a dose of 75 mg/kg, was active. There was a dip followed by rise in blood pressure° . Ethanol (80%) extract of the aerial parts, at a dose of 10 mg/kg, was not blocked by atropine. The extract did not inhibit pressor response of norepinephrine either . Ethanol (95%) extract of the seed, administered intravenously to dogs at a dose of 10 mg/kg, produced a transient effect that was blocked by atropine ". Petroleum ether fraction chromatographed and fraction eluted with chloroform, administered intravenously to rabbits at a dose of 0.80 mg/kg, was inactive. Methanol extract, administered intravenously to dogs and rabbits at a... 

Hypotensive activity. Ethanol (50%) extract of the fresh leaf, administered intragastrically to rats at a dose of 40 mL/kg, was active . 

Hypotensive activity. Methanol (50%) extract of the dried rhizome, administered intravenously to rats at doses of 0.25 and 0.5 g/kg (dry weight of plant), was active ° k Hypothermic activity. Hot water extract of a mixture of Pinellia ternata (Tu), Magnolia obovata (Bk), Perilla frutescens (Aer), Zin ber officinale (Rh), and Poria cocos (Fr) (6, 3, 2, 1, and 5 g, respectively), adminis-... 

Mechanism of Action A synthetic analog of prostaglandin with ocular hypotensive activity. Tiicrapcutic Effect Reduces intraocularpressure(lOP) by increasing the outflow of aqueous humor. 

Use of Bombax ceiba leaves to reduce blood sugar levels is common in North Pakistan Saleem et al. tried an evaluation of the hypotensive activities (and hypoglycemic effect) of the shamimin, a new C-glycosylflavone isolated from this plant. This compound caused 81, 67, and 51%i falls in blood pressure at the doses of 15, 3, and 1 mg/kg, respectively. The effect lasted for 2 to 4 min. Shamimin also produced a significant hypoglycemic effect in Sprague-Dawley rats at the dose of 500 mg/kg the decrease remained constant for the next 4 h. Plasma sugar levels showed a decline of 26%. 

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