Ai-Adrenoceptors, antagonists

Urapidil is a selective ai-adrenoceptor antagonist with an additional central antihypertensive mechanism, mediated by the stimulation of serotonergic (5-HTia) receptors in the brain. It may be used in the treatment of essential, but also acute, peri-operative hypertension. The intravenous administration in the treatment of acute, peri-operative hypertension is not associated with a rise of intracranial pressure, in contrast to various other vasodilators. For this reason, urapidil may be used in neuro-surgical interventions. 

Silodosin is an ai-adrenoceptor antagonist that is being marketed for the treatment of urinary disturbances associated with BPH (Figure 8.80). 

Antidepressant drugs can rarely cause priapism. The agent most often implicated has been trazodone, perhaps because of its ai-adrenoceptor antagonist properties. In general venlafaxine has an inhibitory effect on sexual function, but perhaps, like SSRIs, it can rarely cause priapism (23). 

Yohimbine 2, (ai)-Adrenoceptor antagonist agonist Xylazine reversal... 

Djavan B, Marberger M. A meta analysis on file efficacy and tolerability of ai adrenoceptor antagonists in patients wifii lower urinary tract symptoms suggestive of benign prostatic obstruction. Eur Urol 1999 36 1-13. 

Lee, E., Lee, C., 1997. Clinical comparison of selective and non-selective ai -adrenoceptor antagonists in benign prostatic hyperplasia studies on tamsulosin in a fixed dose and terazosin in increasing doses. Br. J. Urol. 80, 606-611. 

Amsulosin Tamsulosin Tamsulosina Tamsulosine Tamsulosinum, Specific ai-adrenoceptor antagonist. Used in treatment of benign prostatic hypertrophy. Boehringer Ingeltieim Pharm. Inc. Yamanouchi U.S.A. Inc. 

Irrespective of the mechanism of action of tricyclic antidepressants, antagonists of a2 autoreceptors per se might have a beneficial effect in depressive illness, since they facilitate noradrenergic neurotransmission. Phenoxybenzamine, dihydroergotamine and yohimbine, but not the selective ai adrenoceptor antagonist prazosin, have been shown to be synergistic with several antidepressants in decreasing B-adrenoceptor density in rat cerebral cortex.Thus combined administration of an a2 adrenoceptor blocker with other antidepressants may provide a rapid onset therapy.RS 21361 produces a more rapid onset of B-adrenoceptor desensitization by itself than desipramine. 

Nokhodian A, Halabi A, Ebert U, Al-Hamdan Y, Kirch W. Interaction of rifampicin widi bunazosin, an ai-adrenoceptor antagonist, in healthy volunteers. Drug Invest 993>) 6, 362-4. 

Contractions are usually evoked by applying 0.5-s trains of pulses of 110% maximal voltage (train frequency 0.1 Hz pulse frequency 5 Hz pulse duration 0.5 ms) (see Note 4 and Table 2 for more details). The amplitude of each monophasic contraction so induced appears to be determined more by released ATP than noradrenaline (Subheading 1.), as we have found that twitch amplitude is attenuated to a significantly greater extent by PPADS (a P2 receptor antagonist) than by prazosin (an ai-adrenoceptor antagonist) (12). Different stimulation conditions have been described by another laboratory (see Note 5). 

Their effects of Ruscus extract was examined by their local administrations of the different concentrations, or their combinations of Ruscus extract with two sympathetic a-acceptor blocking agents such as ai-adrenoceptor antagonist prazosin (41) (Figure 11) and a2-adrenoceptor antagonist rauwolscine (a-yohimbine. 42) ( Figure 11) of an alkaloid, and one calcium blocker diltiazem (50) (Figure 15). 

A final, important distinction between sibutramine and (7-fenfluramine is that the actions of the former, but not the latter, rest on its modification of both 5-HT and noradrenergic transmission. Thus, the reduction in food intake by sibutramine is partially blocked by ai- or jSi-adrenoceptor antagonists as well as 5-HT2a/2C or 5-HT2b/2c antagonists. In fact, there appears to be a synergistic interaction between these two transmitter systems. This is illustrated by a study of the effects of the selective serotonin... 

Mydriasis is induced by ai-adrenoceptor-mediated contraction of the radial pupillary dilator muscle of the iris. Furthermore, activation of this receptor subtype induces an increased outflow of humor from the eye while /i-adrenoceptor stimulation mediate an enhanced humor production which contributes to an increased intraocular pressure. /3-Adrenoceptor antagonists (/3-blocker) can be used in the treatment of glaucoma. 

The nonselective (i-adrenergic blocking agent that is also a competitive antagonist at ai-adrenoceptors is... 

F., Barlocco, D., Dal Piaz, V., Leonardi, A., Poggesi, E., Fanelli, F., De Benedetti, P. G. Isoxazolo-[3,4-d]-pyridazin-7-(6H)-ones and their corresponding 4,5-disub-stituted-3-(2H)-pyridazinone analogues as new substrates for ai-adrenoceptor selective antagonists synthesis, modeling and binding studies. Bioorg. Med. Chem. 1998, 6, 925-935. 

The effects of a2 agonists can be reversed with the specific 02 adrenoceptor antagonists yohimbine, tolazoline, atipamezole or idazoxan. Yohimbine is an ct2 antagonist with an a2/ i adrenoceptor selectivity of 60 1. Tolazoline is less 2 specific than yohimbine. Atipamezole has an 2/ai specificity that is 200-300 times that of yohimbine. Atipamezole, at a dose rate of 60 pg/ kg, effectively reverses medetomidine action (plasma levels of 1-1.5 ng/ml) (Bettschart-Wolfensberger et al 1999). Doses of 100-160 pg atipamezole have... 

Contraction of the smooth muscle of the prostate gland, prostatic urethra, and bladder neck is also mediated by ai-adrenoceptors, with a, being predominant, and blockade of these receptors relaxes the tissue. For this reason the quinazoline a,-antagonists doxazosin (42), prazosin (43), and terazosin (44) have also found use in treatment of benign prostatic hyperplasia (BPH). However, prazosin. 

In patients with BPH, the most common adverse effects for ai-adrenergic antagonists are related to vasodilation, including dizziness, orthostatic hypotension, headache, and tachycardia, which occurred during the first 2 weeks of treatment (46). Therefore, a dose titration usually is required, especially in patients older than 60 years. These cardiovascular side effects are attributed to a nonselective blockade of ai-adrenoceptors present in vascular smooth muscle in addition to the required blockade of ai-adrenoceptors in prostate. No first-dose effect and fewer vasodilatory adverse events have been reported with the sustained-release formulations, which occur more frequently with the immediate-release formulation At higher doses, orthostatic hypotension occurs more frequently. The first-dose phenomenon of orthostatic hypotension and syncope has been reported occasionally in elderly patients and in those concurrently receiving calcium antagonists, diuretics, and p-blockers. 

In addition to a reversal in potency, a dual-action drug may show equipotency for one activity. Carvedilol (Fig. 6) is a nonselective p-adrenoceptor antagonist with vasodilator activity used in the treatment of hypertension and angina. (iS)-Carvedilol is a potent competitive inhibitor at pi-adrenoceptors, whereas the 7 -enantiomer is considerably less potent, with pA2 values of 9.4 and 3.9 for (S)- and (7 )-carvedilol, respectively [39]. In contrast, the enantiomers are essentially equipotent with respect to ai-adrenoceptor blockade, with pA2 values of 7.87 and 7.79 for the S- and / -enantiomers, respectively [39]. Thus the vasodilator and antihypertensive effects of the drug arise as a result of ai-adrenoceptor blockade of both enantiomers and the pi-blockade from the -enantiomer which prevents reflex tachycardia. Similarly to amosulalol, outlined above, the lack of stereoselectivity with respect to ai-adrenoceptor blockade is presumably associated with the hydroxy group being located in a noncritical region of the molecule for receptor interaction. 

Key Words CBi receptor agonists CBi receptor antagonists cannabidiol 6"-azido-2"-yne-cannabidiol abnoimal-cannabidiol P2X purinoceptors ai-adrenoceptors vanilloid (TRPVl) receptors SR141716A R-(-t)-WIN55212 CP55940 anandamide ATP phenylephrine. 

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