Noscapine

Noscapine (also known as Narcotine, Nectodon, Nospen, Anarcotine and (archaic) Opiane) is a benzylisoquinoline alkaloid, of the phthalideisoquinoline structural subgroup, which has been isolated from numerous species of the family Papaveraceae (poppy family). It lacks significant hypnotic, euphoric, or analgesic effects affording it with very low addictive potential. This agent is primarily used for its antitussive (cough-suppressing) effects. Noscapine is often used as an antitussive medication. A 2012 Dutch guideline, however, does not recommend its use for acute coughing. Nausea Vomiting Loss of coordination Hallucinations (auditory and visual) Loss of sexual drive Swelling of prostate Loss of appetite Dilated pupils Increased heart rate Shaking and muscle spasms Chest pains Increased alertness Loss of any sleepiness Loss of stereoscopic vision Noscapine can increase the effects of centrally sedating substances such as alcohol and hypnotics. The drug should not be taken with any MAOIs (monoamine oxidase inhibitors), as unknown and potentially fatal effects may occur. Noscapine should not be taken in conjunction with warfarin as the anticoagulant effects of warfarin may be increased. The biosynthesis of noscapine in P. somniferum begins with chorismic acid, which is synthesized via the shikimate pathway from erythrose 4-phosphate and phosphoenolpyruvate. Chorismic acid is a precursor to the amino acid tyrosine, the source of nitrogen in benzylisoquinoline alkaloids. Tyrosine can undergo a PLP-mediated transamination to form 4-hydroxyphenylpyruvic acid (4-HPP), followed by a TPP-mediated decarboxylation to form 4-hydroxyphenylacetaldehyde (4-HPAA). Tyrosine can also be hydroxylated to form 3,4-dihydroxyphenylalanine (DOPA), followed by a PLP-mediated decarboxylation to form dopamine. Norcoclaurine synthase (NCS) catalyzes a Pictet-Spengler reaction between 4-HPAA and dopamine to synthesize (S)-norcoclaurine, providing the characteristic benzylisoquinoline scaffold.