Following the discovery of the weak, competitive and reversible acetylcholinesterase (AChE)-inhibiting activity of minaprine (3c) (IC50 = 85 microM on homogenized rat striatum AChE), a series of 3-amino-6-phenylpyridazines was synthesized and tested for inhibition of AChE. A classical structure-activity relationship exploration suggested that, in comparison to minaprine, the critical elements for high AChE inhibition are as follows: (i) presence of a central pyridazine ring, (ii) necessity of a lipophilic cationic head, (iii) change from a 2- to a 4-5-carbon units distance between the pyridazine ring and the cationic head. Among all the derivatives investigated, 3-[2-(1-benzylpiperidin-4-yl)ethylamino]-6-phenylpyridazine (3y), which shows an IC50 of 0.12 microM on purified AChE (electric eel), was found to be one of the most potent anti-AChE inhibitors, representing a 5000-fold increase in potency compared to minaprine.1

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The aim of this study was to assess the performance of the Movement Disorders Society (MDS) criteria for the diagnosis of Parkinson's disease dementia (PDD) in the elderly, and also to evaluate the relevance of applying other tests in this patient population. The MDS criteria include a first short part in checklist form, and a second part which is used as a basis for reference and consists of an in-depth neuropsychological examination. Forty consecutive PD patients presenting with cognitive complaints were enrolled. An assessment was made of the performances of the MDS checklist compared with the MDS exhaustive cognitive examination which was used as a basis for reference, and with other cognitive tests including the Mattis Dementia Rating Scale (MDRS), the French version of the Grober and Buschke test, the verbal fluency test, the Rey-Osterreith complex figure and the paced auditory serial addition test. Out of a total of 40 PD subjects (mean age: 80.5 ± 4.9 years), 20 were diagnosed with PDD according to the checklist and 31 on the basis of the exhaustive examination, i.e. with 11 more patients diagnosed via the latter. The sensitivity of the checklist for the diagnosis of PDD was 0.64, with a specificity of 1.00. The use of the MDRS for PDD diagnosis with a cut-off at ≤ 120 showed a sensitivity of 0.80 and a specificity of 1.00, while at ≤ 132 it displayed a sensitivity of 1.00 and a specificity of 0.444. The specificity of the checklist for the diagnosis of PDD in the elderly was confirmed, but it was lacking in sensitivity. It was also found that the MDRS could be helpful in the diagnosis and screening of PDD.