Clonidine Antihypertensives

The position of substitution is critical. In one position the new group will lead to an enhancement of activity, while in another position it will result in a reduction of activity. For example, the antihypertensive clonidine with its o,o -dichloro substitution is more potent than its m,p-dichloro analogue (Figure 4.3). 

The structures of substituted imidazolines such as the antihypertensives Clonidine and Moxonidine have been studied with B3LYP/6-31- -G(d,p) and BP86/TZ2P DFT methods (Scheme 6) <2006BMC1715>. 

Similar conclusions could be derived from an investigation of antihypertensive clonidine analogs, with respect to their peripheral hypertensive side effects. For a series of clonidine-related imidazolines, log Papp values were determined in -octanol/buffer at pH 7.4, central antihypertensive activities C2s (molar doses that cause a 25% blood pressure decrease, intravenous application) in anesthesized rats, peripheral hypertensive activities C o (molar doses that cause a 60-mm Hg blood pressure increase, intravenous application) in pithed rats (i.e., rats without central nervous system control), binding affinities IC50ai to ai receptors (replacement of prazosin), and binding affinities IC50+ 10 a2 receptors (replacement of clonidine) [86,87],... 

CENTRALLY ACTING ANTIHYPERTENSIVES- CLONIDINE ALPHA-BLOCKERS-PRAZOSIN Small case series indicate that prazosin may -L the antihypertensive effect of clonidine Uncertain at present Monitor BP at least weekly until stable... 

In addition to its use as an antihypertensive, clonidine has been proven useful in a wide variety of conditions. Clonidine has sedative properties and has been used to treat attention-deficit hyperactivity disorder, nicotine and opiate withdrawal, and glaucoma among other uses. Epidural anesthesia has been found to be enhanced by Q2-agonists (20), and clonidine is available in an injectable form for epidural administration. 

In a study with 3427 male and female patients having DBP of 95—109 mm Hg (12—15 Pa), and no clinical evidence of cardiovascular diseases, half of the patients were placebo-treated and half were SC antihypertensive dmg-treated, ie, step 1, chlorothiazide step 2, methyldopa, propranolol [525-66-6], or pindolol [13523-86-9], and step 3, hydralazine, or clonidine [4205-90-7] (86). Overall, when the DBP was reduced below 100 mm Hg (13 Pa), there were more deaths in the dmg-treated group than in the placebo group. The data suggest reduction of blood pressure by antihypertensive dmg treatment that includes a diuretic is accompanied by increased cardiovascular risks. 

Antihypertensive drugp are contraindicated in patients with known hypersensitivity to the individual dm. When an antihypertensive is administered by a trans-derrnal system (eg, clonidine), the system is contraindicated if the patient is allergic to any component of the adhesive layer of the transdermal system. Use of the angiotensin II receptor antagonists during the second and third trimester of pregnancy is contraindicated... 

Figure 27. Comparison of the relationship between antihypertensive and sympathomimetic activity and sedation and inhibition of gastric secretion of clonidine and two derivatives (St 600 and St 608). The antihypertensive activity was tested in genetic hypertensive rats. The sympathomimetic activity was measured as blood pressure increase in spinal rats. The sleep effect in chicks was tested according to the method in Reference 50, and the gastric secretion in rats was measured according to the method in Reference 57.

Antihypertensive Alpha methyldopa Clonidine Guanethidine Propranolol Reserpine... 

Clonidine (Catapres). Clonidine, an antihypertensive medication that decreases serotonin availability through a mechanism distinct from cyproheptadine, has also been tested in the treatment of AN. Unfortunately, clonidine does not appear to promote weight gain in anorexia patients. In addition, clonidine may further exacerbate the low blood pressure that AN patients commonly experience. Consequently, clonidine has no role in the treatment of AN. 

Clonidine raises systemic blood pressure and heart rate by stimulating o -adrenorecep-tors in certain parts of the CNS, and it is used mainly as an antihypertensive agent. Clonidine is used in various forms of hypertonic illnesses and for stopping hypertensive attacks. It is also used in ophthahnological practice for open-angle glaucoma. Synonyms of clonidine are hemiton, catapres, and clofelin. 

Drugs that may be affected by dexmethylphenidate or racemic methylphenidate include antihypertensive agents, pressor agents, coumarin anticoagulants, anticonvulsants, tricyclic antidepressants, selective serotonin reuptake inhibitors, and clonidine. 

Clonidine is an agonist at a - and o 2-adreno-ceptor subtypes. It reduce the sympathetic tonus and is thereby a useful antihypertensive drug. Clonidine can induce sedation, depression and peripheral side effects like a dry mouth. Unspecific a-adrenoceptor blocking agents like tricyclic antidepressants can reduce the antihypertensice effect of clonidine. 

Clonidine has been put forward for many years as the prototype of selective agonists of central o 2-adrenoceptor agonists. More recently it has been shown to be a mixed agonist of both 2- and 11-receptors in the central nervous system. It is an effective antihypertensive which has been used on a large scale for several decades. Its use has greatly declined in recent years because of its poor tolerability when compared with more modern antihypertensives. Sedation, dry mouth and sexual impotence are the most obvious side-effects. 

Clonidine, a central acting antihypertension agent (q 2 adrenergic agonist) is classically cited as an antimigraine drug although it is less effective than beta-blockers. 

C. Trimethaphan is a ganglionic blocking agent that will lower blood pressure very rapidly. Hydralazine is a vasodilator hydrochlorothiazide and spironolactone are diuretics and methyldopa is a sympatholytic acting in the central nervous system. All of these drugs are used clinically as antihypertensive agents. None work as rapidly as trimethaphan. Clinically, however, either nitroprusside or clonidine is used much more commonly than trimethaphan in this situation. 

Two important antihypertensive agents, a-methyldopa and clonidine, act predominantly in the brain (Fig. 20.2D). Although the details of their actions may differ in some respects, their antihypertensive activity is ultimately due to their ability to decrease the sympathetic outflow from the brain to the cardiovascular system. 

Guanabenz (Wytensin) and guanfacine Tenex) are two drugs with considerable structural similarity to clonidine. These agents also are central aj-agonists and exhibit an antihypertensive profile similar to that of clonidine. 

The antihypertensive activity of clonidine can be ascribed solely to a decrease in the sympathetic activity transmitted from the brain to the peripheral vasculature. After clonidine administration, direct measurements of sympathetic nerve activity show that electrical discharge is reduced in a number of sympathetic nerves, including the cardiac, splanchnic, and cervical nerves. 

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