Adrenergic receptors antagonists

Risperidone (11) was also included among a a 1-adrenergic receptor antagonists to study a quantitative structure-activity relationship (99BMC2437). A pharmacophore model for atypical antipsychotics, including 11, was established (00MI41). An increased plasma level of 11 and 9-hydroxyrisperidone (12) was observed in combination with paroxetine (01 MI 13). The effect of vanlafaxine on the pharmacokinetics of 11 was reported (99MI13). 

Therapeutic Function 8eta-adrenergic receptor antagonist... 

Agonists as well as antagonists of (3-adienergic receptors are used for the treatment of a variety of conditions. (3-Adrenergic receptor antagonists belong to the most frequently used classes of dtugs. 

Clinically used p-adrenergic receptor antagonists ( P-blockers ) are either px-selective (e.g. bisoprolol, metoprolol, atenolol, betaxolol) or non-selective,... 

Non-selective P-adrenergic receptor antagonists (e.g. propranolol) can suppress tachycardia and tremor in patients with hyperthyroidism or tremor caused by... 

Antagonism of several characteristic effects of amphetamine and cocaine by the alpha adrenergic receptor antagonist prazosin is a most recent example of noradrenergic mechanisms in the actions of psychomotor stimulants (Tessel and Barrett 1986). We investigated whether or not prazosin may attenuate the disruptive effects of amphetamine on social and aggressive behavior in mice and squirrel monkeys (Miczek, unpublished observations). Pretreatment with prazosin (0.4 mg/kg) attenuated the disruption of attack... 

The major circulating hormones that influence vascular smooth muscle tone are the catecholamines epinephrine and norepinephrine. These hormones are released from the adrenal medulla in response to sympathetic nervous stimulation. In humans, 80% of catecholamine secretion is epinephrine and 20% is norepinephrine. Stimulation of cy-adrenergic receptors causes vasoconstriction. The selective a,-adrenergic receptor antagonist, prazosin, is effective in management of hypertension because it causes arterial and venous smooth muscle to relax. 

Vasodilators. Hydralazine causes direct relaxation of arteriolar smooth muscle. An important consequence of this vasodilation, however, is reflex tachycardia (T CO). It may also cause sodium retention (T plasma volume). The resulting increase in CO tends to offset effects of the vasodilator. Therefore, these drugs are most effective when administered along with sympathetic agents such as P-adrenergic receptor antagonists, which prevent unwanted compensatory responses by the heart. 

ADRB2) antagonists (salbutamol, formoterol) airway responsiveness to beta-2-adrenergic receptor antagonists in asthmatics (24) in asthmatic (23) and severity of asthma (92)... 

The answer is i. (Hardman, p 2312) Timolol is a p-adrenergic receptor antagonist that does not show selectivity for pi or p2 adrenoceptors ... 

Esmolol hydrochloride is a competitive p-adrenergic receptor antagonist it is selective for pT adrenoceptors. In contrast to pindolol, esmolol has little intrinsic sympathomimetic activity, and it differs from propranolol in that it lacks membrane stabilizing activity Of all of the p-adrenergic blocking drugs, this compound has the shortest duration of action because it is an ester, it is hydrolyzed rapidly by plasma esterases and must be used by the intravenous route Esmolol is approved only for the treatment of supraventricular arrhythmias... 

Clinical Trials. In Phase I studies, good documentation and additional investigations should be standard practice. Serious reactions are pretty unusual in these studies, which will detect only very common ADRs, in particular those that are pharmacologically mediated (e.g., bradycardia with beta adrenergic receptor antagonists). 

Scheme 6.1 Chemical structures of adrenergic receptor antagonists for generation of antitarget pharmacophores class I (a) and class II (b).

Figure 6.3 Common-feature pharmacophores ofala adrenergic receptor antagonists [16]. Onto each pharmacophore the reference has been mapped, (a) Class I pharmacophore model aligned to prazosin, (b) class II pharmacophore model aligned to compound 10.

Montorsi, M., Menziani, M.C., Cocchi, M., Fanelli, F. and De Benedetti, P.G. (1998) Computer modeling of size and shape descriptors of al-adrenergic receptor antagonists and quantitative structure-affinity / selectivity relationships. Methods, 14, 239-254. 

Menziani, M.C., Montorsi, M., De Benedetti, P.G. and Karelson, M. (1999) Relevance of theoretical molecular descriptors in quantitative structure-activity relationship analysis of alphal-adrenergic receptor antagonists. Bioorganic el Medicinal Chemistry, 7, 2437-2451. 

Prazosin volume, thereby reduces cardiac output Alpha-adrenergic receptor antagonist, inhibits symphathetic... 

Ono H, Mishima A, Ono S, Fukuda H, Vasko MR (1991) Inhibitory effects of donidine and tizanidine on release of substance P from slices of rat spinal cord and antagonism by a-adrenergic receptor antagonists. Neuropharmacology 30, 585-589... 

The directly acting vasodilators, with the exception of calcium channel antagonists and sympathetic nervous system depressants, receive the bulk of attention in this chapter. Other chapters offer additional information on diuretics (see Chapter 21), the renin-angiotensin system (see Chapter 18), adrenergic receptor antagonists (see Chapter 11), and the calcium channel antagonists (Chapter 19). 

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