Tranylcypromine sulfate

A solution containing 167 grams of stabilized styrene and 183 grams of ethyl diazoacetate is cooled to 0°C and dropped into 83.5 grams of styrene with stirring, in a dry nitrogen atmosphere, at 125° to 135°C, This produced the ester ethyl 2-phenylcyclopropanecar-boxylate. 

A solution of the above ester (207.8 grams) and 64.5 grams of sodium hydroxide in 80 cc of water and 600 cc of ethanol is refluxed for 9 hours. The carboxylic acid of 2-phenyl-cyclopropane is liberated with 200 cc of concentrated hydrochloric acid. The 2-phenyl-cyclopropanecarboxylic acid contains 3 to 4 parts of the trans isomer to 1 part of the cis isomer. The acid is recrystallized from hot water. The pure trans isomer comes out as crystalline material (solid) while the cis isomer stays in solution. 

A solution of 4.62 grams of 2-phenylcyclopropanecarboxylic acid in 15 cc of dry benzene is refluxed with 4 cc of thionyl chloride for 5 hours, the volatile liquids are removed and the residue once more distilled with benzene. Fractionation of the residue yields the carbonyl chloride of 2-phenylcyclopropane. 

The almost dry residue is cooled to 0°C and made strongly alkaline with a 50% potassium hydroxide solution. The amine is extracted into several portions of ether, dried over potassium hydroxide, the solvent removed, and the base fractioned. Reaction of the base with a half-molar quantity of sulfuric acid gives the sulfate. 

Tedeschi, R.E. U.S. Patent 2,997,422 August 22, 1961 assigned to Smith Kline French Laboratories 

Sodium hydroxide Sodium azide Sulfuric acid 

Ethyl diazoacetate Thionyl chloride Hydrogen chloride 

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Tranylcypromine sulfate is an antidepressant drug and an inhibitor of MAO. Its antidepressant effect is probably due to the accumulation of NE in the brain as a consequence of inhibition of the enzyme. The other MAO I currently used as an antidepressant is phenelzine sulfate. 

FIGURE 14.9 Performance of short column ultrahigh pressure nano LC system at 10 /rL/min for the separation of tranylcypromine sulfate, perphenazine, and their impurities. Nano LC may be operated at 10 times optimum column flow rate and achieve ultrahigh throughput and reproducibility. Short column (3 cm x 150 /mi inner diameter) was packed with 1.8 /im C18 particles. Solvent A was water with 0.4% ammonia solvent B was acetonitrile with 0.4% ammonia. Gradient 0 to 1 min, 3 to 10% B 1 to 1.3 min, 10 to 35% B, 1.3 to 3.5 min, 35 to 90% B held at 90% B through 4.9 min and then returned to 3% B. Column head pressure was 7200 psi. 

Preliminary studies suggest that MAOIs are effective in juvenile and adult ADHD. In a controlled trial of clorygline (MAOI-A) and tranylcypromine sulfate (mixed), Zametkin et al. (1985) reported a significant reduction in ADHD symptoms with minimal adverse effects. Eeigin et al. (1996) conducted a controlled trial of 10 mg of selegiline (which at low doses is a specific MAOI-B) in children with ADHD and Tourette s syndrome. Selegiline was well tolerated and was associated... 

Monoamine oxidase (MAO) inhibitors, nonselective (Types A,B) phenelzine sulfate tranylcypromine sulfate... 

Tranylcypromine Sulfate, USP. Tranylcypromine sulfate. ( )-(ran.r-2-phcnylcyclopropylamine sulfate (Parnate), was synthesized to be an amphetamine analogue (visualize Ihc nr-mcihyl of amphetamine condensed onto Ihe fi-carbon atom). It d(x .s have. some amphetamine-like proper-lie.s. which may be why it has more immediate CNS stimulant effects than agents that act by MAO inhibition alone. For MAO inhibition, there may be two components to Ihc... 

Monoamine oxidase inhibitors (MAOI) Neurotransmitters norepinephrine, dopamine, epinephrine, and serotonin are inactive by the enzyme monoamine oxidase. MAOI inhibits monoamine oxidase, resulting in a rise in the levels of these neurotransmitters. MAOI are isocarboxazid (Marplan), phenelzine sulfate (Nardil), and tranylcypromine sulfate (Parnate). 

Monoamine oxidase inhibitor (MAOI) antidepressants have been in use for nearly 40 years. At the present time, they are viewed as second- or third-line antidepressant medications for reasons of both efficacy and safety. The available MAOIs are phenelzine sulfate (Nardil), isocarboxazid (Marplan), and tranylcypromine sulfate (Parnate). Two additional MAOI antidepressants, moclobemide and brofaromine, are approved for use in Europe and/or Canada. 

NB See also Abdel-Aleem H, El-Ashmawy MB, Belai F, El-Amam AA and Brittain HG, Tranylcypromine Sulfate, APDS, 25, 501-533 (1997) (no specific reference). 

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