Atropine distribution

After intravenous dosing, atropine distributes rapidly, with only 5% remaining in the blood compartment after 5 min (Bcrghem et at., 1980). The apparent volume of distribution (V i) is 1-1.7 liters/kg. Atropine is partly metabolized in the liver by microsomal monooxygenases to noratropine, tropinc, atropine-A/-oxide, and tropic acid (Van der Meer et at., 1983) and partly excreted unchanged in the urine. Elimination kinetics can be fitted to a two-compartment model with a clearance of 5,9-6,8 ml/kg/min and a half-life of 2.6—4.3 hr in the elimination phase (Aaltonen etal., 1984 Kanto etal., 1981 Virtanen etal., 1982). Since the renal plasma clearance (656 18 ml/min) was found to approach the renal plasma flow (712 38 ml/min), tubular... 

As a result of the widespread global distribution of solanaceous plants (atropine containing members of the potato family), a variety of cultures have employed them Similar poisoning occurred among Colonial troops in Virginia in 1676. The affected soldiers needed confinement for eleven days (a surprisingly long... 

All the belladonna alkaloids are well absorbed from the GIT, from the site of injection and the mucous membrane. They are distributed throughout the body and cross the blood-brain barrier. About 50% of the atropine is metabolized in liver and remaining portion is excreted unchanged in urine. Atropine cross the placental barrier and is secreted in milk and saliva. 

Atropine and the other tertiary agents are widely distributed in the body. Significant levels are achieved in the CNS within 30 minutes to 1 hour, and this can limit the dose tolerated when the drug is taken for its peripheral effects. Scopolamine is rapidly and fully distributed into the CNS where it has greater effects than most other antimuscarinic drugs. In contrast, the quaternary derivatives are poorly taken up by the brain and therefore are relatively free—at low doses—of CNS effects. 

The octanol-water partition coefficient (Kow), characterizing distribution of a non-ionized compound between an octanol (o) and an immiscible aqueous (w) layer, may function as a measure of lipophilicity, that is often listed as its logarithmic value (log P). Therefore, log P may be used as a predictor of extractability in LLE. Table 1 presents log P values of TA calculated by the Molinspiration software [25] using SMILES notation for chemical structures. The SMILES concept is addressed in the next section [26], Conformity of calculated (calc.) and experimental (exp.) log P values is satisfying, as exemplarily shown for atropine (1.83 exp. [27] 1.77 calc.) and scopolamine (0.98 exp. [22] 1.05 calc.). 

Until recently, anatoxin-a was the only naturally occmring alkaloid possessing the 9-azabicy-clo[4.2.1]nonane ring skeleton, in contrast with the many examples of the similar 8-azabicy-clo[3.2.1]octane ring systems found in the diverse and widely distributed atropine alkaloids (i.e., ferruginine and cocaine). As a result of the combination of its biological potency and its rare structure,... 

The belladonna alkaloids are absorbed rapidly from the gastrointestinal tract. They also enter the circulation when applied locally to mucosal surfaces. Only limited absorption occurs from the intact skin. Atropine disappears rapidly from the blood and is distributed throughout the entire body. Most is excreted in the urine within the first 12 h, in part unchanged. Only about 1% of an oral dose of scopolamine is eliminated as such in the urine. Traces of atropine are found in various secretions, including milk. The total absorption of quaternary ammonium derivatives of the alkaloids after an oral dose is only about 10-25 percent (10,11) nevertheless, some of these compounds can cause mydriasis and cycloplegla if applied to the eye. 

Wlobladh (102) presented data on the distribution of atropine labeled randomly with newborn pups. 

Evertsbusch, V., Gelling, E.H.K. 1953 Distribution and Excretion of Radioactivity in Mice Following the Administration of C -Labeled Atropine. Fed. Proc. 12 319. 

Radioactive Atropine. I. Distribution and Excretion Patterns In the Mouse. Arch. Internat. Fharmacodyn. Therap. 105 175-192. 

Physiological Distribution of Atropine In the Rat. Pharmacol. Blochem. Behav. 2 843-845 ... 

Antimuscarinics having a quaternary ammonium group are incompletely absorbed from the gut since these are completely ionized. The tertiary amine antimuscarinics are readily absorbed from the gut. The presence of food may reduce absorption. Quaternary ammonium antimuscarinics exhibit poor lipid solubility, do not cross the blood-brain barrier, and thus exhibit minimal central nervous system (CNS) effects. Also due to their poor lipid solubility they do not penetrate the eye and are unlikely to appear in the milk. Atropine and other tertiary amines are capable of crossing the CNS. Atropine is capable of crossing the placenta and has been stated to distribute into milk in small quantities. It is oxidized primarily in the liver. Atropine is apparently metabolized in the liver to tropic acid, tropine, and possibly esters of tropic acid and glucuronide conjugate. 

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