There exist reports of NMS occurring in patients prescribed venlafaxine in isolation [Lu et al. 2006]. NMS has generally been associated with high doses of antipsychotic medication as opposed to the low dose in this case although Lazarus and colleagues did conclude that NMS appeared not to be dose dependent [Viejo et al. 2003; Lazarus et al. 1989]. We considered the potential impacts of both hepatitis infection and methadone in the
development of NMS in this case but were unable to find any clear associations for either. It does not seem unreasonable to suggest that as a serotonergic enhancer, methadone may be involved in central dopaminergic inhibition similar to that seen with antidepressants Inhibitors,research,lifescience,medical and may therefore Inhibitors,research,lifescience,medical have played some role in the development of NMS in the above case. Footnotes Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Conflict of interest statement: GW has accepted transport and accommodation payments to attend
educational meetings sponsored by both AstraZeneca and Bristol-Myers Squibb. RB has accepted transport and accommodation Inhibitors,research,lifescience,medical payments to attend an educational meeting sponsored by Pfizer. Contributor Information Gary Woods, Ards Community Hospital, South Eastern Health and Social Care Trust, Newtownards, UK. Catherine Taggart, Windsor House, Belfast City Hospital, Belfast Health and Social Care Trust, Lisburn Road, Belfast BT9 7AB, UK. Robert Boggs, Substitute Prescribing Service, Belfast Health and Social Care Trust, Belfast, UK. Ian Cadden, Royal Victoria
Hospital, Belfast Health and Social Care Trust, Belfast, UK.
AZD8931 molecular weight clozapine is an antipsychotic drug that was first manufactured in 1959 and introduced into clinical practice in the 1970s. It has Inhibitors,research,lifescience,medical been shown to be more effective in the treatment of schizophrenia than typical antipsychotics [Wahlbeck et al. 2000]. It is the drug of choice for treating treatment refractory Inhibitors,research,lifescience,medical schizophrenia. It is the most effective antipsychotic for severe, refractory schizophrenia [Barnes, 2011]. Clozapine is a widely used atypical antipsychotic, and it has a complex and not entirely understood mechanism of action. It has a pharmacological profile and side effects that are different to those of other typical and atypical antipsychotic drugs; in fact, it interacts with several subtypes of dopaminergic (D1, D2, D3, D4), serotonergic (5-HT1A, 5-HT2A, 5-HT2C, 5- HT3, 5-HT6, 5-HT7), adrenergic isothipendyl (1, 2), histamine (H1) and muscarinic (M1) receptors [Raggi et al. 2004]. It has been hypothesized that this high affinity of clozapine for dopamine D4 receptors, rather than the D2 receptors, is the origin of its superiority. There is a 2.8% risk of granulocytopenia when taking clozapine and a 0.6% risk of agranuloctosis [Loebel et al. 1992]. Other well-known side effects concern sedation in 39% of patients [Safferman et al. 1991], and precipitation of seizures.