Propranolol base

Fig. 3.4 Permeability profiles for (a) warfarin (acid), (b) propranolol (base) and (c) morphine (ampholyte) based on a BBB PAMPA model (plON) composed of animal brain extract of lipids. The data (unpublished) were analyzed with the pCEL-X program (plON), with the refined parameters indicated in the three frames. In all three cases, there was evidence for the permeation of charged...

Fig. 2.1. Lipophilicity profiles for diclofenac (acid), propranolol (base) and morphine (ampholyte). Dashed lines indicate the pH range where molecule may partition in its ionized form.

Fig. 1 Theoretical proposed representation of the signal to noise in the cortical networks as affected by propranolol, based upon the findings of Hasselmo et al (1997) on the effects of norepinephrine in the cortex. Black arrows indicate a greater response to the most dominant signal input, such as representation of an attended stimulus, which may be suppressed by noradrenergic blockade. White arrows indicate the response to nondominant signal input, such as intrinsic or associative fiber inputs, the noise in the model, which may increase with noradrenergic blockade, proposed to be how problems without an immediately accessible answer may be solved more readily in this condition or how patients with impaired flexibility of network access may benefit in a more general manner in this condition.

The interaction of a-naphthol and epichlorohydrin in the presence of aqueous alkali gives 2,3-epoxypropyl-a-naphthyl ether which upon treatment with isopropylamine affords the rupture of the epoxy ring thereby forming the propranolol base and this ultimately yields the official compound with HCl. 

Interaetion of 1-naphthol with epiehlorohydrin affords a glyeidie ether whieh upon treatment with isopropylamine aids in the opening of the oxirane ring yielding the propranolol base and this on being treated with a known quantity of hydroehlorie acid gives the official compound. 

Table 1 Physicochemical Characteristics and Skin Permeation Fluxes of S-Enantiomer and Racemate (RS) of Propranolol Base...

A chiral electrochemical sensor for propranolol based on multi-walled carbon nanotubes/ionic liquids nanocomposite, 105,... 

Cromakalim (137) is a potassium channel activator commonly used as an antihypertensive agent (107). The rationale for the design of cromakalim is based on P-blockers such as propranolol (115) and atenolol (123). Conformational restriction of the propanolamine side chain as observed in the cromakalim chroman nucleus provides compounds with desired antihypertensive activity free of the side effects commonly associated with P-blockers. Enantiomerically pure cromakalim is produced by resolution of the diastereomeric (T)-a-meth5lben2ylcarbamate derivatives. X-ray crystallographic analysis of this diastereomer provides the absolute stereochemistry of cromakalim. Biological activity resides primarily in the (—)-(33, 4R)-enantiomer [94535-50-9] (137) (108). In spontaneously hypertensive rats, the (—)-(33, 4R)-enantiomer, at dosages of 0.3 mg/kg, lowers the systoHc pressure 47%, whereas the (+)-(3R,43)-enantiomer only decreases the systoHc pressure by 14% at a dose of 3.0 mg/kg. 

Fig. 2-13. The effect of acid and base concentration on the resolution of propranolol on teicoplanin CSP (250 x 4.6 mm) in the new polar organic mode. The flow rate was 2.0 mL min at ambient temperature (23 °C).

An example of the effect of acid and base concentration on the separation of propranolol is shown in Fig. 2-13. In this case, the baseline separation is achieved by adjusting the concentration without changing the acid/base ratio. 

Treat severe or troublesome autonomic signs and symptoms with a non-selective (3-blocker such as propranolol 20 to 40 mg four times daily. Titrate the 3-blocker dose based on signs and symptoms. 

It is convenient to summarize the various reactions in a box diagram, such as Fig. 4.1 [17,275,280], illustrated with the equilibria of the weak base, propranolol. In Fig. 4.1 is an equation labeled pA °et. This constant refers to the octanol pKa, a term first used by Scherrer [280]. When the concentrations of the uncharged and the charged species in octanol are equal, the aqueous pH at that point defines p which is indicated for a weak acid as... 

The two-component lipid models were also characterized in the absence of sink conditions (Table 7.8). Comparisons between models 7.0 (Table 7.7) and 1.0 (Table 7.5) suggest that negative charge in the absence of sink causes the permeabilities of many of the bases to decrease. Exceptions are quinine, prazosin, primaquine, ranitidine, and especially metoprolol. The inclusion of 0.6% PA causes Pe of metoprolol to increase nearly 10-fold, to a value twice that of propranolol, a more lipophilic molecule than metoprolol (based on the octanol-water scale). Naproxen and ketoprofen become notably more permeable in the two-component system. Surprisingly, the neutral progesterone becomes significantly less permeable in this system. 

Figure 7.41 Gradient pH profiles for three weak bases with double-sink conditions, 20% wt/vol soy lecithin in dodecane (a) verapamil (pKa 9.07) (b) propranolol (pKa 9.53) (c) metoprolol (pKa 9.56).

FIGURE 1.21 Schild plots for the antagonism by propranolol of the actions of noradrenaline (open circles) and isoprenaline (closed circles) on the contractile force of the isolated atrium of the guinea pig. The x shows the value obtained with noradrenaline as agonist but in the presence of cocaine (20 pM). (From Furchgott, R. F., Handbook of Experimental Pharmacology, Vol. 23, 1972, pp. 283-335 based on the results of Blinks, J. R Ann. N.Y.Acad. Sci., 139, 673-685, 1967.)... 

The RIA-procedure for propranolol is solely based on antisera derived from conjugates through the asymmetric carbon (i.e., the optical carbon) as shown in the above chemical structures. Perhaps it could be possible that the stereospecificity of propranolol is caused due to the conformation of the drug-hapten in relation to the carrier protein to a great extent, through this hypothesis remains to be ascertained scientifically. 

Levitt, D.G., PKQuest a general physiologically based pharmacokinetic model — introduction and application to propranolol, BMC Clin. Pharmacol, 1, 5, 2002. 

Propranolol, ketamine, phenylalanine, tryptophan, lactic acid RP-HPLC column coated with chiral Schiff base 2 mM CUSO4 in water —CH3CN (85 15) 213... 

Specific Sociai Anxiety Disorder, Acute Phase Treatment. Different strategies have evolved for treating specific social anxiety disorder versus generalized social anxiety disorder. Less complicated is the management of the specific subtype. Exposure-based psychotherapy is a mainstay of treatment, and as-needed medication doses prior to scheduled performances are also widely used. Preferred agents for performance anxiety are alprazolam or propranolol. 

Ahlquist, in 1948, first proposed that noradrenaline could produce its diverse physiological effects by acting on different populations of adrenoceptors, which he termed a and ft receptors. This classification was based upon the relative selectivity of adrenaline for the a receptors and isoprenaline for the ft receptors drugs such as phentolamine were found to be specific antagonists of the a, and propranolol for the ft receptors. 

Fig. 3.9 Bioavailability (f) of propranolol (1), betaxolol (2), metoprolol (3) and talinolol (4) found in vivo in man compared to that predicted based solely on hepatic extraction.

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