Scopolamine structure

Anisodine is a natural TTA that represents a derivative of the scopolamine structure mono-hydroxylated at the tropic acid moiety (Fig. 1). Similar to anisodamine it was extracted from Chinese herb Anisodus tanguticus (Maxim.) Pascher and also exhibits al-AR blocking properties and non-specific anticholinergic effects. Accordingly, in China anisodine is used for the therapy of the same indications as described for anisodamine, most often to treat transmissible shock. Toxicity and side effects of anisodine are smaller than those for atropine, scopolamine and anisodamine [5],... 

FIG. 18 Chemical structures of (a) acetylcholine chloride, (b) carbamylcholine chloride, (c) carba-myl-y8-methylcholine chloride, (d) acetyl-/i-methylcholine chloride, (e) tetramethylammonium chloride, (f) tetraethylamonium chloride, (g) succinylcholine chloride, (h) hexamethonium chloride, (i) scopolamine hydrobromide, 0 atropine sulfate, (k) homatropine hydrochloride, and (1) tubocurar-ine chloride. 

Figure 14.1.4 The molecular structure of nitroglycerin, angina attacks or scopolamine (Fig. 14.1.5) to protect against motion sickness are...

ATROPINE, SCOPOLAMINE AND DITRAN Treatment Studies with Atropine, Scopolamine and Ditran COMPARISONS OF BELLADONNOID PROPERTIES Structures and Names of Belladonnoids Studied... 

Rutaecarpine (46) is the major alkaloid found in Evodia rutaecarpa (Juss.) Benth., and activities relevant to AD have been identified with the extract and with rutaecarpine. Dehydroevodiamine (47), another alkaloid from the same species, inhibited AChE in vitro, and reversed scopolamine-induced memory impairment in rats and increased cerebral blood flow in vivo in cats, a property which would supplement its usefulness in AD. The structures of (46) and (47) and tacrine (28) have been used as templates for the development of a series of synthetic compounds which have been evaluated for their antiChE activity. These were found to be inhibitory against both AChE and BuChE with A -(2-phenylethyl)-A -[(12Z)-7,8,9,10-tetrahydroazepino [2,l- ]quinazolin-12(6//)-ylidene] amine (48) showing higher affinity for BuChE. 

The best known of the muscarinic blocking drugs are the belladonna alkaloids, atropine (Atropine) and scopolamine (Scopolamine). They are tertiary amines that contain an ester linkage. Atropine is a racemic mixture of DL-hyoscyamine, of which only the levorotatory isomer is pharmacologically active. Atropine and scopolamine are parent compounds for several semisynthetic derivatives, and some synthetic compounds with little structural similarity to the belladonna alkaloids are also in use. All of the antimuscarinic compounds are amino alcohol esters with a tertiary amine or quaternary ammonium group. 

The action of scopolamine, then, seems to correspond with that of atropine, except that the central nervous system is here depressed, while the action on the peripheral structures is of shorter duration. It depresses the brain in very small quantities 0.5 mg is generally sufficient to induce... 

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.). 

Fig. 7 Selected biotransformation products of diverse tropane alkaloids identified by LC-MS/MS approaches. Depicted metabolites are only an exert of those presented by Chen et al. for anisodamine (Ada) [6], atropine (Atr) [51], and scopolamine (Sep) [7] as well as by He et al. for benztropine (Benz) [59]. Structures were identified from in vivo and in vitro samples following diverse modes of MS/MS analysis as discussed in the section Biotransformation studies...

The 80 MHz H n.m.r spectrum of 7V-(cylcopropylmethyl)scopolaminium bromide in D20 has been analysed and the conclusions have been compared with those from X-ray crystal-structure studies.19 They were consistent with the equatorial position of the cyclopropylmethyl group, as shown in (17). All protons in symmetrical positions (1 and 5, 6 and 7, 2 and 4) of the tropane ring were found to be magnetically non-equivalent, as in scopolamine hydrobromide and in atropine. This was attributed to the different shielding effects that arise from the aromatic substituent which is attached to the asymmetric centre of the tropic acid moiety. The carboxyl group of the tropate residue was found to be opposite to H-3. 

The on-line coupling of CE with electrospray ionization mass spectrometry (CE-ESI-MS) allows high separation efficiency together with high sensitivity and selectivity as well as molecular structural information. A CE-UV-ESI-MS method was developed for the analysis of hoscyamine, scopolamine, and other tropane derivatives [131]. The differentiation of hyoscyamine from littorine, commonly encountered in plant material, was demonstrated using in-source collision-induced dissociation. The developed method was applied to the analysis of these alkaloids in Belladonna leaf extract and in Datura Candida x D. awreahairy root extract. Recently, CE coupled with electrochemiluminescence detection has been used for the determination of atropine and scopolamine in Flos daturae [132]. 

Hyoscine (scopolamine) is structurally related to atropine. It differs chiefly in being a central nervous system depressant, although it may sometimes cause excitement. Elderly patients cire often confused by hyoscine and so it is avoided in their anaesthetic premedication. Mydriasis is also briefer than with atropine. 

Acid hydrolysis of this new alkaloid with 10% HCl gave (-)-tropic acid and a hydrolysate whose spectral data, H-and C-NMR and electron-impact (El) MS, were completely identical with that of 3a, 6p-dihydroxytropane HCl. This evidence indicated the hydrolysate to be the enantiomer of 3a, 6P-dihydroxytropane HCl. Concomitant with the structural confirmation by preparing the alkaloid from (-)-scopolamine HBr using Raney Ni, this new tropane alkaloid was characterized as 7P-hydroxyhyoscyamine [12]. 

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