Tropine benzilate (also known as glipin, BAT or T.B.) is an ester formed between tropine and benzilic acid. Like its structural relatives such as atropine and scopolamine, tropine benzilate is considered a muscarinic antagonist, meaning it binds to and blocks muscarinic acetylcholine receptors in the nervous system and various tissues.

The substance was first described in 1936 and was shown to relax smooth muscle and block signals from the vagus nerve. It was also later shown to block stomach acid secretion in dogs.

It is a chemical deliriant similar to two related substances, namely 3-quinuclidinyl benzilate (aka QNB or agent Buzz) and CS-27349. However, BAT differs from these two agents in that it was never enlisted in a psychochemical warfare programme by Edgewood Arsenal (as an incapacitating agent) and is endowed with medically useful properties.

Another compound with which T.B. shares a striking similarity is called Tropenzile. T.B. sans the tertiary hydroxy group goes by name Tropacine.

Atropine and scopolamine (c.f. PC12047005) are natural alkaloids with a substantially similar structure to BAT, but differ in that they are formed from tropic acid and not benzilic acid. Tropic acid has a chiral carbon whereas benzilic acid is achiral. Whereas tropic acid is a natural product, benzilic acid is not known to exist in nature.

Tropine benzilate is less commonly sold as a tertiary amine, but is usually encountered as the quaternary amine Flutropium bromide. {It is worth making the distinction that although BAT can be used to make Flutropium bromide, one encounters the wrong stereochemistry about the bridgehead nitrogen when employing this method of synthesis. It is unknown what effect this would have on the resultant pharmacology. To make it correctly one has to use Norglipin [16444-19-2]. This same compound also finds use in the synthesis of Trospium chloride.}

Alpha-stereochemistry is used to make BAT which mimics atropine. Beta-stereochemistry would be more closely expected to mimic tropacocaine, although alpha stereochemistry is stronger. Compared to tropacocaine, it is not known if beta-BAT has affinity toward biogenic amine transporters, although this was not documented to have been reported in the literature. Further reading Lednicer teaches that amides are more resistant to metabolic degradation than esters because they are not subject to esterases. However, this was with reference to local anesthetics (e.g. lidocaine) and Antiarrhythmics. Although BAT-amide does not appear in the pubchem database, c.f. QNB-amide.Kiyoshi Taniguchi, et al. JPH09328469 (1997 to Fujisawa Pharmaceutical Co Ltd). endo-8-Methyl-8-azabicyclo[3.2.1]octan-3-amine has instead found use in the synthesis of a compound that is called SS16.Alessandro Bartolini, et al. WO1994001435 (Abiogen Pharma SRL). This is made from [3307-39-9].

The ester between tropine and clofibric acid gave rise to a compound that is called SM-25. Many more such agents were described in the patent. A more well characterized compound appearing in the literature is called SM-21 Maleate: [155059-42-0].Ghelardini et al (1997) Antinociceptive profile of 3-α-tropanyl-(2-Cl)-acid phenoxybutyrate (SM-21): a novel analgesic with a presynaptic cholinergic mechanism of action. J.Pharmacol.Exp.Ther. 282 430 PMID: 9223584Ghelardini et al (2000) Pharmacological identification of SM-21, the novel σ2 antagonist. Pharmacol.Biochem.Behav. 67 659 PMID: 11164098Matsumoto and Mack (2001) (±)-SM 21 attenuates the convulsive and locomotor stimulatory effects of cocaine in mice. Eur.J.Pharmacol. 417 R1 PMID: 11301071Matsumoto et al (2007) Effects of UMB24 and (+/-)-SM 21, putative σ2-preferring antagonists, on behavioral toxic and stimulant effects of cocaine in mice. PLoS One 86 86 PMID: 17241657Ishima and Hashimoto (2012) Potentiation of nerve growth factor-induced neurite outgrowth in PC12 cells by ifenprodil: the role of σ-1 and IP3 receptors. J Diabetes Res 7 e37989 PMID: 22655093Ghelardini, C., Galeotti, N., Gualtieri, F., Scapecchi, S., Bartolini, A. (December 1997). "3‐α‐tropanyl 2‐(4‐Cl‐phenoxy)butyrate (SM 21): A Review of the Pharmacological Profile of a Novel Enhancer of Cholinergic Transmission". CNS Drug Reviews. 3 (4): 346–362. doi:10.1111/j.1527-3458.1997.tb00332.x. Another one is called PG-9 Fb: [156143-26-9] Maleate salt: [155649-00-6].Ghelardini, Carla; Galeotti, Nicoletta; Bartolini, Alessandro; Furukawa, Shoei; Nitta, Atsumi; Manetti, Dina; Gualtieri, Fulvio (1998). "Memory Facilitation and Stimulation of Endogenous Nerve Growth Factor Synthesis by the Acetylcholine Releaser PG-9". The Japanese Journal of Pharmacology. 78 (3): 245–251. doi:10.1254/jjp.78.245.Ghelardini C, Galeotti N, Gualtieri F, Marchese V, Bellucci C, Bartolini A. Antinociceptive and antiamnesic properties of the presynaptic cholinergic amplifier PG-9. J Pharmacol Exp Ther. 1998;284(3):806-16. PMID: 9495837.Ghelardini, C., Galeotti, N., Romanelli, M. N., Gualtieri, F., Bartolini, A. (March 2000). "Pharmacological Characterization of the Novel ACh Releaser α‐tropanyl 2‐(4‐bromophenyl)propionate (PG‐9)". CNS Drug Reviews. 6 (1): 63–78. doi:10.1111/j.1527-3458.2000.tb00138.x.

Synthesis Tropine benzilate may be synthesized by reacting tropine with methyl benzilate in a transesterification reaction.Example 4 in

See also Trospium chloride

References