noscapine and Stroke

Noscapine is a phthalide isoquinoline alkaloid with antitussive activity. Noscapine protects oligodendroglia from ischemic and chemical injury, binds to bitter taste receptors, antagonizes the bradykinin and histaminergic systems, which may be of benefit in treatment of multiple sclerosis. Noscapine normalizes axonal transport and exerts significant therapeutic efficacy in animal models of Parkinson's Disease and Amyotrophic Lateral Sclerosis. Noscapine exerts neuroprotective effects on oxygen- and glucose-deprived fetal cortical neuronal cells and reduces ischemic brain damage in neonatal rat pups. Pilot clinical studies indicated some beneficial effects of noscapine in stroke. Noscapine harbours anxiolytic activity and methyl-noscapine blocks small conductance SK channels, which is beneficial in alleviating anxiety and depression. Noscapine exerts anticholinesterase activity and acts inhibitory on the inflammatory transcription factor NF-κB, which may be harnessed in treatment of Alzheimer's Disease. With its blood-brain barrier traversing features and versatile actions, noscapine may be a promising agent in the armamentarium against neurodegenerative and psychiatric diseases.

Topics: Alzheimer Disease; Amyotrophic Lateral Sclerosis; Animals; Bradykinin; Histamine Antagonists; Humans; Immunomodulating Agents; Ion Channels; Mental Disorders; Multiple Sclerosis; Neurodegenerative Diseases; Neuroprotective Agents; Noscapine; Oligodendroglia; Parkinsonian Disorders; Receptors, G-Protein-Coupled; Signal Transduction; Stroke

Recently, noscapine was reported as anticancer drug. Unlike, colchicine and podophyllotoxin, noscapine did not depolymerize microtubules even at stoichiometric concentrations but rather only mitigated their dynamics. Other microtubule-interacting chemotherapeutics, although quite effective, have therapy-limiting toxicities including immunosuppression and peripheral neuropathies. Recurrent cancers often become resistant. Noscapine however remains effective in some such instances, e.g., taxane-resistant ovarian cancer. Noscapine and analogs also do not show signs of neurotoxicity or immunosuppression. In addition, 9-bromo noscapine, Red-9-Br-Nos and other analogs were characterized for their structure and further studied in detail. On the other hand, noscapine was shown to be neuroprotective in mouse model of neurodegenerative disease and in stroke patients. Like low doses of colchicine, noscapine and its analog 9-Br-Noscapine also show anti-inflammatory activities. There are indications of a preventive use of noscapine in ischemiareperfusion injury and fibrosis. The entire biosynthetic pathway of noscapine is encoded as gene cluster within 401 kilo bases of genomic DNA, opening up opportunities for the large-scale biotechnological production of noscapine for medicinal needs. Thus, noscapine and its derivatives (noscapinoids) might be cost-effective and safe components for cancer chemotherapy. Owing to its low toxicity, it also might be useful for preventive use in high-risk situations. This brief review is an update of current research activity and patents on noscapine and its analogs.

Topics: Antineoplastic Agents; Antitussive Agents; Apoptosis; Humans; Noscapine; Stroke; Structure-Activity Relationship

Given its manifold potential therapeutic applications and amenability to modification, noscapine is a veritable "Renaissance drug" worthy of commemoration. Perhaps the only facet of noscapine's profile more astounding than its versatility is its virtual lack of side effects and addictive properties, which distinguishes it from other denizens of Papaver somniferum. This review intimately chronicles the rich intellectual and pharmacological history behind the noscapine family of compounds, the length of whose arms was revealed over decades of patient scholarship and experimentation. We discuss the intriguing story of this family of nontoxic alkaloids, from noscapine's purification from opium at the turn of the 19th century in Paris to the recent torrent of rationally designed analogs with tremendous anticancer potential. In between, noscapine's unique pharmacology; impact on cellular signaling pathways, the mitotic spindle, and centrosome clustering; use as an antimalarial drug and cough suppressant; and exceptional potential as a treatment for polycystic ovarian syndrome, strokes, and diverse malignancies are catalogued. Seminal experiments involving some of its more promising analogs, such as amino-noscapine, 9-nitronoscapine, 9-bromonoscapine, and reduced bromonoscapine, are also detailed. Finally, the bright future of these oftentimes even more exceptional derivatives is described, rounding out a portrait of a truly remarkable family of compounds.

Topics: Alkaloids; Animals; Antineoplastic Agents; Centrosome; Chemistry, Pharmaceutical; Drug Evaluation, Preclinical; Female; Humans; Male; Microtubules; Neoplasms; Noscapine; Papaver; Plant Extracts; Stroke; Warfarin

Stroke is the third leading cause of death in most developed countries. Therefore, a need exists for its treatment. Considering the role that is played by bradykinin in pathogenesis of neuronal injury, it has been suggested that bradykinin antagonists may be useful in the treatment of neurological patients. As noscapine can act as an antagonist of bradykinin and can effectively reduce brain injury after hypoxic-ischemic insult in neonatal rats, the present work was carried out to investigate its effectiveness in a clinical setting.. Noscapine was administrated orally to ten acute ischemic stroke patients, and the degree of brain injury was evaluated by computed tomography scan and clinical observation. The control group (n=10) did not receive noscapine treatment.. Our study showed that noscapine effectively improved clinical prognosis and reduced the mortality rate down to 20% compared with 80% in the control group. Our patients did not show any specific side effects due to noscapine.. It is concluded that oral noscapine can be an effective drug for reducing the mortality rate in stroke; however, further study with a larger number of patients is needed to determine its full potential in stroke.

Topics: Aged; Aged, 80 and over; Animals; Bradykinin; Brain Edema; Female; Humans; Male; Middle Aged; Noscapine; Rats; Stroke