Safinamide in neurological disorders and beyond: Evidence from preclinical and clinical studies.

The discovery and development of safinamide, an alpha-aminoamide, has been a valuable addition to the existing clinical management of Parkinson's disease (PD). The journey of safinamide dates back to the year 1983, when an alpha-aminoamide called milacemide showed a weak anticonvulsant activity. Milacemide was then structurally modified to give rise to safinamide, which in turn produced robust anticonvulsant activity. The underlying mechanism behind this action of safinamide is attributed to the inhibition of voltage gated calcium and sodium channels. Moreover, owing to the importance of ion channels in maintaining neuronal circuitry and neurotransmitter release, numerous studies explored the potential of safinamide in neurological diseases including PD, stroke, multiple sclerosis and neuromuscular disorders such as Duchenne muscular dystrophy and non-dystrophic myotonias. Nevertheless, evidence from multiple preclinical studies suggested a potent, selective and reversible inhibitory activity of safinamide against monoamine oxidase (MAO)-B enzyme which is responsible for degrading dopamine, a neurotransmitter primarily implicated in the pathophysiology of PD. Therefore, clinical studies were conducted to assess safety and efficacy of safinamide in PD. Indeed, results from various Phase 3 clinical trials suggested strong evidence of safinamide as an add-on therapy in controlling the exacerbation of PD. This review presents a thorough developmental history of safinamide in PD and provides comprehensive insight into plausible mechanisms via which safinamide can be explored in other neurological and muscular diseases.

Sinapic Acid Alleviates Oxidative Stress and Neuro-Inflammatory Changes in Sporadic Model of Alzheimer's Disease in Rats.

The role of oxidative stress, neuro-inflammation and cholinergic dysfunction is already established in the development of Alzheimer's disease (AD). Sinapic acid (SA), a hydroxylcinnamic acid derivative, has shown neuro-protective effects. The current study evaluates the neuro-protective potential of SA in intracerebroventricular streptozotocin (ICV-STZ) induced cognitive impairment in rats. Male Wistar rats were bilaterally injected with ICV-STZ. SA was administered intragastrically once daily for three weeks. Rats were divided into sham, ICV-STZ, STZ + SA (10 mg/kg), STZ + SA (20 mg/kg) and SA per se (20 mg/kg). Behavioral tests were assessed on day 0 and 21 days after STZ. Later, rats were sacrificed for biochemical parameters, pro-inflammatory cytokines, choline acetyltransferase (ChAT) expression and neuronal loss in the CA1 region of the hippocampus. The results showed that SA 20 mg/kg significantly (p < 0.05) improved cognitive impairment as assessed by Morris water maze and passive avoidance tests. SA 20 mg/kg reinstated the altered levels of GSH, MDA, TNF-α and IL-1ß in the cortex and hippocampus. STZ-induced decreased expression of ChAT and neuronal loss were also significantly (p < 0.05) improved with SA. Our results showed that SA exhibits neuro-protection against ICV-STZ induced oxidative stress, neuro-inflammation, cholinergic dysfunction and neuronal loss, suggesting its potential in improving learning and memory in patients of AD.

Attitude and opinion towards essential medicine formulary.

OBJECTIVE: The Delhi State Drug Policy was adopted in 1994 following which the first Essential Medicines List (EML) was developed in 1996. The Delhi State Essential Medicines Formulary was brought out in 1997. A need was felt to revise the formulary to match with the EML as the EML is renewed every 2 years. MATERIALS AND METHODS: A survey was undertaken to elicit the opinions of the doctors practicing in the state on the usefulness of the formulary before revising and printing the updated version. The survey covered dispensaries, 10-20 bedded hospitals, 100-bedded hospitals and two tertiary care hospitals. Discussions were focused on questionnaires on attitudes toward adopting Essential Medicines Formulary using a 10-point scale. RESULTS: Of the 200 doctors approached, only 90 doctors completed the questionnaire. Sixty-nine respondents (76.6%) had received the copy of the formulary. Most practitioners welcomed the formulary and were satisfied with the coverage and selection of the medicines. Most respondents (76.9%) agreed that a well-developed formulary would improve the quality of the public health care system, although they had reservations about the authority, relevance and effect on professional autonomy. CONCLUSION: About 74% of the respondents used the formulary in clinical practice as a source of medicine information, which makes its regular revision necessary.