- Email: [email protected]
Dementia accompanying motor neuron disease — 7 cases
S320
P4. Degenerative and neurological disorders
Methods: Children and adolescents 8 to 18 years old with ADHD were randomized to treatment with placebo or atomoxetine administered twice daily as a weight-adjusted total dose of 0.5 mglkglday, 1.2 mg/kg/day, 1.8 mg/kg/day for an 8-week period. ADHD symptoms, social functioning, and family functioning were assessed using the Attention-Deficit Hyperactivity Rating Scale-IV-Parent Versiombtvestigator Administered and Scored (ADHDRS-IV-Parent:Inv) and the Conners’ Parent Rating ScaleRevisedShort Form (CPRS-R:S). Broader family and psychosocial functioning was assessed via the Child Health Questionnaire (CHQ) and the ADHD Impact Module (AIM). Results: 297 children (M 212/F 85; median age 10.8 years) were randomized to therapy (placebo N = 84, 0.5 mg/kg/day N = 44, 1.2 mgkgday N = 84, 1.8 mgkg/day N = 85). At baseline all groups were comparable on demographic and symptom severity measures. At endpoint the mean (SD) change from baseline in ADHDRS-IV-Parent:Inv was significantly greater for the atomoxetine 1.2 and 1.8 m&g&y groups compared with placebo (placebo -5.8 [10.9], 0.5 mg/kg/day -9.9 [14.6], 1.2 mgikg/day -13.6 [14.0], 1.8 mg/kgday -13.5 [14.5]; pairwise comparisons with placebo p < .OOl for the 1.2 and 1.8 mgkgday doses). Outcomes on the CPRS-R:S were similar, and outcomes were also similar between younger and older children. Social functioning and family functioning as assessed by CHQ and AIM were also significantly improved in the atomoxetine-treated patients compared with placebo. Atomoxetine was well tolerated, with discontinuations due to adverse events < 5% for all groups. Conclusion: Atomoxetine was markedly superior to placebo in reducing ADHD symptoms. Evidence of a graded dose-response was observed, and symptom reduction appeared to be maximal at 1.2 mgkgday with no apparent benefit at the 1.8 mgikgday dose. Atomoxetine was also associated with improvements in overall social and family functioning compared with placebo. Treatment with atomoxetine was well tolerated. References [l] American Psychiatric Association. (1994) Diagnostic and Statistical
Manual of Mental Disorders: DSM IV, Fourth Edition. 4th ed. Washington, DC: American Psychiatric Association. [2] Biedennan J, Mick E, Prince J, Bostic JQ, Wilens TE, Spencer TJ et al. (1999) Systematic chart review of the pharmacologic treatment of comorbid attention deficit hyperactivity disorder in youth with bipolar disorder. J Child Adolesc Psychopharmacol 9 (4), 247-256. [3] Hechtman L. (1996) Attention-deficit hyperactivity disorder. In: Hechtman L, editor. Do They Grow Out of It? Long-term Outcomes of Childhood Disorders. Washington, DC: American Psychiatric Press, 17-38.
doses of donepezil for memory enhancement, and several bipolar patients became hype/manic when taking donepezil, particularly with evening administration.3 In a naturalistic longitudinal follow-up study we are now investigating donepezil’s long-term effects on mood and cognitive function in affective illness, including the safety and tolerability of treatment for memory loss, dry mouth, and constipation. Methods: Non-demented bipolsr/unipolar outpatients who took donepezil 2.5-10 mg/day for >6 months were studied. Chart reviews with ratings for memory dysfunction, sleep, mood stability, and CGI scale were conducted for patients with monthly clinical monitoring. Contributory factors to cognitive function, affective stability, and drug interactions were assessed. Results: Preliminary findings for 38 patients (25 women, 13 men; mean age = 47.7 + 10.2 years) taking donepezil (6.7 & 3.0 mg) for 20.8 It 10.6 months indicate that most report sustained improvement in short-term memory. Memory benefits usually faded within several days of discontinuation, but tended to recur shortly after restarting donepezil. Concentration was also reported to improve by several patients. Patients who had first degree relatives with Alzheimer’s disease tended to respond only to high dose donepezil (10 mg), admitted to heavy (~-20 pack year) smoking histories, and subsequently reported gradually increasing memory dysfunction over one to two years. Several of these ‘diminishing responders” - considered non-demented at the beginning of the study - have now been diagnosed with early stage Alzheimer’s disease. Major side effects of gastrointestinal distress (20%) and insomnia (12%) were usually easily managed with dose reduction and morning administration. Donepezil elevated mood to the level of hypomania in several bipolar patients, but was not associated with induction of depression, change in mood cycling, or other symptomatic recurrence. Several patients reported enhanced sexual drive with donepezil. Nine patients quit treatment or could not arrange for insurance coverage of donepezil (since they weren’t diagnosed with Alzheimer’s disease). In affectively ill patients complaining of Conclusions: psychotropic-associated memory loss, long-term treatment with donepezil enhances memory and is well tolerated. Anticholinergic hypersensitivity manifested by psychotropic-associated memory complaints may be an early predictor of Alzheimer’s disease in affective illness patients with a family history of dementia. Diminishing long-term memory benefits from donepezil in affective illness may indicate a potentially heritable progressive decline in cholinergic function. References
mj
Long-term memory and mood effects of donepezil in affective illness
EM. Jacobsen, L. Comas-D&. George Washington University School of Medicine Department of Psychiaw and Behavioml Sciences, Transcultuml Mental Health Institute, Washington, D.C., USA Background: Recent evidence suggests that depression often precedes the development of both Alzheimer’si and vascular dementias, and that mild cognitive impairment heralds early-stage Alzheimer’s Disease.* We reported robust short-term memory enhancement over 3-6 weeks with the acetylcholinesterase inhibitor donepezil in stabilized affectively ill patients complaining of psychotropic-associated memory impairment.3 However, patients having a parent with Alzheimer’s disease required higher
[I] Berger AK, et al. Neurology 1999; 53: 1998-2002. [2] Morris JC, et al. Arch Neurology 2001; 58: 397-405. [3] Jacobsen FM, Comas-Diaz L: J Clin Psychiatry 1999; 60: 698-704.
Ip.4.0101
Dementia accompanying disease - 7 cases
motor neuron
R. Marquard’ , R. Miillerz, M. Wada3, A. Kurz*. ‘Department of Psychiatq BKH TaujkirchenIVils; 2Department of Psychiatry, Technische Universitiit M&hen, Germany; Department of Psychiatry, Kyoto University Japan In an epidemiological survey, dementia was reported in 2-6% of the ALS cases. There is an ongoing discussion if ALS associated frontal lobe dementia is a variant of ALS, a variant of FLD or a new disease entity.
P4. Degenerative and neurological disorders In this study we 1. report seven cases of D-MND. 2. The the frequency of D-MND in dementia and frontal lobe dementia is shown. 3. Epidemiologic data of D-MND are compared with Pick, FLD and DAT. We consecutively recruited 1000 outpatients with the diagnosis of dementia. 7 (0.7%) suffered from dementia with MND. There was no family history of dementia or MND except one male patient who had a desorientated father of 88. The average onset of dementia was 54.4 years. All patients had frontal lobe symptomatology with personality changes, apathy and progressive aphasia. None of them had apraxia, agnosia or visual/spatial disturbances. Dementia was mild to moderate according to an average MMSE of 25 (21-29). All patients developed neurological symptoms after an interval of 28 (7-54) months. Neurogenic muscle atrophy and bulbar symptoms were apparent in all cases. No extrapyramidal symptoms were found. The electromyography was specific for MND. The EEG remained normal. All patients had cranial CT or MRI scans. Four showed a mild frontal atrophy. Three had a normal brain. SPECT was done in one case (female, 47 years), which showed reduced cerebral blood flow in highfrontal area. The duration of the illnes was limited in all cases by progressive MND. The age of death was 58.9 (49-68) years. Compared to Pick and FLD cases no sign&and difference was found in sex ratio, age at onset and age of diagnosis. D-MND patients were less demented according to MMSE. Compared to DAT cases, D-MND patients were sign&and younger and less demented. Among 1000 dementia cases D-MND was more frequent than Pick’s disease, Lewybody disease or CJD and accounted for 30% of all forms of frontal lobe. dementia. According to the relative high frequency of D-MND, frontal lobe- and subcortical pathology seems to be common in MND and might be detected by neuropsychological and PET investigations. As the neuropathology of D-MND is identical with ALS, D-MND is rather the cortical manifestation of ALS than a new disease entity.
S321
(ADAS-cog), administered by a rater blinded to the patient’s treatment, at baseline and weeks 4 and 12. Results: Baseline demographic characteristics were similar with mean baseline MMSE scores of 21.5 f 4.1 and 20.7 f 5.0 for patients randomized to donepezil (n = 56) and rivastigmine (n = 55), respectively. The mean overall age was 74.4 with 59% females. 89.3% donepezil- and 69.1% rivastigmine-treated patients completed the study @ = 0.009) with 10.7% and 21.8% of patients, respectively, discontinuing due to AEs. The following AEs occurred in at least 5% of patients in either group and at least twice the rate of the comparator group (% donepezil vs % rivastigmine, respectively): nausea (10.7 vs 41.8), vomiting (7.1 vs 23.6), headache (7.1 vs 18.2) anorexia (1.8 vs 9.1), abnormal dreams (7.1 vs 1.8), back pain (7.1 vs 0), somnolence (1.8 vs 5.5) and urinary tract infection (5.4 vs 0). 87.5% and 47.3% of donepeziland rivastigmine-treated patients, respectively, remained on the maximum dose to the last study visit. Physicians and caregivers reported significantly higher total satisfaction/ease of use scores for donepezil treatment compared to rivastigmine treatment at Weeks 4 (p i 0.0001) and 12 @ < 0.05). Both treatment groups showed similar improvements from baseline on blinded ADAScog scores with mean changes at Week 12 (OC) of -0.90 and - 1.05 for donepezil and rivastigmine groups, respectively. Conclusions: The results of this first direct comparative trial of two cholinesterase inhibitors suggest that donepezil was better tolerated compared with rivastigmine. Consistent with the tolerability differences and rivastigmine’s required titration and twice daily dosing, physicians and caregivers favored the use of donepezil relative to rivastigmine. Although both agents improved cognition to a similar extent, fewer rivastigmine-treated patients were able to reach and be maintained on the maximum approved dosage levels.
IP.4.0121 Effect of naloxone treatment on ATP-ase’s activities of synaptic plasma membranes from rat hippocampus
m[
Donepezil compared to rivastigmine in Alzheimer’s disease: Similar efficacy but better tolerability and physician and caregiver satisfaction in a multinational randomized trial
C. Hock, D.G. Wilkinson, P Passmore, R. Bullock, SW. Hopker, R. Smith, F.C.V Potocnik, CM. Maud, I. Englebrecht, V Mastey, R. Bahra, E. Schwam, J. Ieni. University of Zurich, Lengstmsse 31, CH 8029 Zurich, Switzerland Objectives: To compare the tolerability, physician and caregiver satisfaction and efficacy of donepezil and rivastigmine in Alzheimer’s disease (AD) patients. Methods: 111 patients with possible or probable, mild to moderate AD (Mini-Mental State Examination [MMSE] 10-26) from three countries were randomized to receive open label doses of either rivastigmine or donepezil escalated to the highest approved doses (donepezil 10 mg once daily; rivastigmine 6 mg twice daily), as recommended in the respective product labeling, for 12 weeks. Adverse events (AEs) were assessed throughout the trial. Physicians and caregivers rated satisfaction/ease of use with assigned treatment for each patient using Like&type questionnaires including items assessing ease of use, dosing frequency and titration at weeks 4 and 12. Cognition was assessed using the Alzheimer’s Disease Assessment Scale - cognitive subscale
RF. Villa, E. Devecchi, A. Gorini. University of Pavia, Department of Physiological-Pharmacological CellularMolecular Sciences, Division of Pharmacology and Pharmacological Biotechnologies, Labomtory of Neurochemistry and Molecular Medicine, Pavia, Italy Naloxone is a competitive antagonist of morphine, acting on opiate receptors. The effect of in vi00 administration of naloxone on energy-consuming ATP-ases was studied in two types of synaptic plasma membranes (s.p.m.) from rat hippocampus. The ATP-ase’s enzymes related to ions homeostasis (Na, K, Ca, Mg ions) of s.p.m. are involved in physiological regulation of presynaptic nerve endings homeostasis and related to post-synaptic activities. The maximum rates of following enzymes were assayed on s.p.m. (type I, II) of hippocampus of male control Wistar rats aged 4 months and treated ones with effective dose of naloxone (i.m., 12 @kg, sacrifice after 30 min from injection): Na’, K+-ATPase, CaCC, Mg*-ATPaae, Mg*-ATPase, Low and High al-lhiity Ca*-ATPase; the activity of Acetylcholinesterase (AchE) was also evaluated. In control animals, enzyme activities assayed on s.p.m. (type I and II) are higher on s.p.m, of II type, because this fraction is more enriched in s.p.m. The treatment with naloxone increased AChE and Mg*-ATP-ase activities in s.p.m. of II type. The increased catalytic properties of these enzyme systems by naloxone indicate the interference of this drug on
P4. Degenerative and neurological disorders
Methods: Children and adolescents 8 to 18 years old with ADHD were randomized to treatment with placebo or atomoxetine administered twice daily as a weight-adjusted total dose of 0.5 mglkglday, 1.2 mg/kg/day, 1.8 mg/kg/day for an 8-week period. ADHD symptoms, social functioning, and family functioning were assessed using the Attention-Deficit Hyperactivity Rating Scale-IV-Parent Versiombtvestigator Administered and Scored (ADHDRS-IV-Parent:Inv) and the Conners’ Parent Rating ScaleRevisedShort Form (CPRS-R:S). Broader family and psychosocial functioning was assessed via the Child Health Questionnaire (CHQ) and the ADHD Impact Module (AIM). Results: 297 children (M 212/F 85; median age 10.8 years) were randomized to therapy (placebo N = 84, 0.5 mg/kg/day N = 44, 1.2 mgkgday N = 84, 1.8 mgkg/day N = 85). At baseline all groups were comparable on demographic and symptom severity measures. At endpoint the mean (SD) change from baseline in ADHDRS-IV-Parent:Inv was significantly greater for the atomoxetine 1.2 and 1.8 m&g&y groups compared with placebo (placebo -5.8 [10.9], 0.5 mg/kg/day -9.9 [14.6], 1.2 mgikg/day -13.6 [14.0], 1.8 mg/kgday -13.5 [14.5]; pairwise comparisons with placebo p < .OOl for the 1.2 and 1.8 mgkgday doses). Outcomes on the CPRS-R:S were similar, and outcomes were also similar between younger and older children. Social functioning and family functioning as assessed by CHQ and AIM were also significantly improved in the atomoxetine-treated patients compared with placebo. Atomoxetine was well tolerated, with discontinuations due to adverse events < 5% for all groups. Conclusion: Atomoxetine was markedly superior to placebo in reducing ADHD symptoms. Evidence of a graded dose-response was observed, and symptom reduction appeared to be maximal at 1.2 mgkgday with no apparent benefit at the 1.8 mgikgday dose. Atomoxetine was also associated with improvements in overall social and family functioning compared with placebo. Treatment with atomoxetine was well tolerated. References [l] American Psychiatric Association. (1994) Diagnostic and Statistical
Manual of Mental Disorders: DSM IV, Fourth Edition. 4th ed. Washington, DC: American Psychiatric Association. [2] Biedennan J, Mick E, Prince J, Bostic JQ, Wilens TE, Spencer TJ et al. (1999) Systematic chart review of the pharmacologic treatment of comorbid attention deficit hyperactivity disorder in youth with bipolar disorder. J Child Adolesc Psychopharmacol 9 (4), 247-256. [3] Hechtman L. (1996) Attention-deficit hyperactivity disorder. In: Hechtman L, editor. Do They Grow Out of It? Long-term Outcomes of Childhood Disorders. Washington, DC: American Psychiatric Press, 17-38.
doses of donepezil for memory enhancement, and several bipolar patients became hype/manic when taking donepezil, particularly with evening administration.3 In a naturalistic longitudinal follow-up study we are now investigating donepezil’s long-term effects on mood and cognitive function in affective illness, including the safety and tolerability of treatment for memory loss, dry mouth, and constipation. Methods: Non-demented bipolsr/unipolar outpatients who took donepezil 2.5-10 mg/day for >6 months were studied. Chart reviews with ratings for memory dysfunction, sleep, mood stability, and CGI scale were conducted for patients with monthly clinical monitoring. Contributory factors to cognitive function, affective stability, and drug interactions were assessed. Results: Preliminary findings for 38 patients (25 women, 13 men; mean age = 47.7 + 10.2 years) taking donepezil (6.7 & 3.0 mg) for 20.8 It 10.6 months indicate that most report sustained improvement in short-term memory. Memory benefits usually faded within several days of discontinuation, but tended to recur shortly after restarting donepezil. Concentration was also reported to improve by several patients. Patients who had first degree relatives with Alzheimer’s disease tended to respond only to high dose donepezil (10 mg), admitted to heavy (~-20 pack year) smoking histories, and subsequently reported gradually increasing memory dysfunction over one to two years. Several of these ‘diminishing responders” - considered non-demented at the beginning of the study - have now been diagnosed with early stage Alzheimer’s disease. Major side effects of gastrointestinal distress (20%) and insomnia (12%) were usually easily managed with dose reduction and morning administration. Donepezil elevated mood to the level of hypomania in several bipolar patients, but was not associated with induction of depression, change in mood cycling, or other symptomatic recurrence. Several patients reported enhanced sexual drive with donepezil. Nine patients quit treatment or could not arrange for insurance coverage of donepezil (since they weren’t diagnosed with Alzheimer’s disease). In affectively ill patients complaining of Conclusions: psychotropic-associated memory loss, long-term treatment with donepezil enhances memory and is well tolerated. Anticholinergic hypersensitivity manifested by psychotropic-associated memory complaints may be an early predictor of Alzheimer’s disease in affective illness patients with a family history of dementia. Diminishing long-term memory benefits from donepezil in affective illness may indicate a potentially heritable progressive decline in cholinergic function. References
mj
Long-term memory and mood effects of donepezil in affective illness
EM. Jacobsen, L. Comas-D&. George Washington University School of Medicine Department of Psychiaw and Behavioml Sciences, Transcultuml Mental Health Institute, Washington, D.C., USA Background: Recent evidence suggests that depression often precedes the development of both Alzheimer’si and vascular dementias, and that mild cognitive impairment heralds early-stage Alzheimer’s Disease.* We reported robust short-term memory enhancement over 3-6 weeks with the acetylcholinesterase inhibitor donepezil in stabilized affectively ill patients complaining of psychotropic-associated memory impairment.3 However, patients having a parent with Alzheimer’s disease required higher
[I] Berger AK, et al. Neurology 1999; 53: 1998-2002. [2] Morris JC, et al. Arch Neurology 2001; 58: 397-405. [3] Jacobsen FM, Comas-Diaz L: J Clin Psychiatry 1999; 60: 698-704.
Ip.4.0101
Dementia accompanying disease - 7 cases
motor neuron
R. Marquard’ , R. Miillerz, M. Wada3, A. Kurz*. ‘Department of Psychiatq BKH TaujkirchenIVils; 2Department of Psychiatry, Technische Universitiit M&hen, Germany; Department of Psychiatry, Kyoto University Japan In an epidemiological survey, dementia was reported in 2-6% of the ALS cases. There is an ongoing discussion if ALS associated frontal lobe dementia is a variant of ALS, a variant of FLD or a new disease entity.
P4. Degenerative and neurological disorders In this study we 1. report seven cases of D-MND. 2. The the frequency of D-MND in dementia and frontal lobe dementia is shown. 3. Epidemiologic data of D-MND are compared with Pick, FLD and DAT. We consecutively recruited 1000 outpatients with the diagnosis of dementia. 7 (0.7%) suffered from dementia with MND. There was no family history of dementia or MND except one male patient who had a desorientated father of 88. The average onset of dementia was 54.4 years. All patients had frontal lobe symptomatology with personality changes, apathy and progressive aphasia. None of them had apraxia, agnosia or visual/spatial disturbances. Dementia was mild to moderate according to an average MMSE of 25 (21-29). All patients developed neurological symptoms after an interval of 28 (7-54) months. Neurogenic muscle atrophy and bulbar symptoms were apparent in all cases. No extrapyramidal symptoms were found. The electromyography was specific for MND. The EEG remained normal. All patients had cranial CT or MRI scans. Four showed a mild frontal atrophy. Three had a normal brain. SPECT was done in one case (female, 47 years), which showed reduced cerebral blood flow in highfrontal area. The duration of the illnes was limited in all cases by progressive MND. The age of death was 58.9 (49-68) years. Compared to Pick and FLD cases no sign&and difference was found in sex ratio, age at onset and age of diagnosis. D-MND patients were less demented according to MMSE. Compared to DAT cases, D-MND patients were sign&and younger and less demented. Among 1000 dementia cases D-MND was more frequent than Pick’s disease, Lewybody disease or CJD and accounted for 30% of all forms of frontal lobe. dementia. According to the relative high frequency of D-MND, frontal lobe- and subcortical pathology seems to be common in MND and might be detected by neuropsychological and PET investigations. As the neuropathology of D-MND is identical with ALS, D-MND is rather the cortical manifestation of ALS than a new disease entity.
S321
(ADAS-cog), administered by a rater blinded to the patient’s treatment, at baseline and weeks 4 and 12. Results: Baseline demographic characteristics were similar with mean baseline MMSE scores of 21.5 f 4.1 and 20.7 f 5.0 for patients randomized to donepezil (n = 56) and rivastigmine (n = 55), respectively. The mean overall age was 74.4 with 59% females. 89.3% donepezil- and 69.1% rivastigmine-treated patients completed the study @ = 0.009) with 10.7% and 21.8% of patients, respectively, discontinuing due to AEs. The following AEs occurred in at least 5% of patients in either group and at least twice the rate of the comparator group (% donepezil vs % rivastigmine, respectively): nausea (10.7 vs 41.8), vomiting (7.1 vs 23.6), headache (7.1 vs 18.2) anorexia (1.8 vs 9.1), abnormal dreams (7.1 vs 1.8), back pain (7.1 vs 0), somnolence (1.8 vs 5.5) and urinary tract infection (5.4 vs 0). 87.5% and 47.3% of donepeziland rivastigmine-treated patients, respectively, remained on the maximum dose to the last study visit. Physicians and caregivers reported significantly higher total satisfaction/ease of use scores for donepezil treatment compared to rivastigmine treatment at Weeks 4 (p i 0.0001) and 12 @ < 0.05). Both treatment groups showed similar improvements from baseline on blinded ADAScog scores with mean changes at Week 12 (OC) of -0.90 and - 1.05 for donepezil and rivastigmine groups, respectively. Conclusions: The results of this first direct comparative trial of two cholinesterase inhibitors suggest that donepezil was better tolerated compared with rivastigmine. Consistent with the tolerability differences and rivastigmine’s required titration and twice daily dosing, physicians and caregivers favored the use of donepezil relative to rivastigmine. Although both agents improved cognition to a similar extent, fewer rivastigmine-treated patients were able to reach and be maintained on the maximum approved dosage levels.
IP.4.0121 Effect of naloxone treatment on ATP-ase’s activities of synaptic plasma membranes from rat hippocampus
m[
Donepezil compared to rivastigmine in Alzheimer’s disease: Similar efficacy but better tolerability and physician and caregiver satisfaction in a multinational randomized trial
C. Hock, D.G. Wilkinson, P Passmore, R. Bullock, SW. Hopker, R. Smith, F.C.V Potocnik, CM. Maud, I. Englebrecht, V Mastey, R. Bahra, E. Schwam, J. Ieni. University of Zurich, Lengstmsse 31, CH 8029 Zurich, Switzerland Objectives: To compare the tolerability, physician and caregiver satisfaction and efficacy of donepezil and rivastigmine in Alzheimer’s disease (AD) patients. Methods: 111 patients with possible or probable, mild to moderate AD (Mini-Mental State Examination [MMSE] 10-26) from three countries were randomized to receive open label doses of either rivastigmine or donepezil escalated to the highest approved doses (donepezil 10 mg once daily; rivastigmine 6 mg twice daily), as recommended in the respective product labeling, for 12 weeks. Adverse events (AEs) were assessed throughout the trial. Physicians and caregivers rated satisfaction/ease of use with assigned treatment for each patient using Like&type questionnaires including items assessing ease of use, dosing frequency and titration at weeks 4 and 12. Cognition was assessed using the Alzheimer’s Disease Assessment Scale - cognitive subscale
RF. Villa, E. Devecchi, A. Gorini. University of Pavia, Department of Physiological-Pharmacological CellularMolecular Sciences, Division of Pharmacology and Pharmacological Biotechnologies, Labomtory of Neurochemistry and Molecular Medicine, Pavia, Italy Naloxone is a competitive antagonist of morphine, acting on opiate receptors. The effect of in vi00 administration of naloxone on energy-consuming ATP-ases was studied in two types of synaptic plasma membranes (s.p.m.) from rat hippocampus. The ATP-ase’s enzymes related to ions homeostasis (Na, K, Ca, Mg ions) of s.p.m. are involved in physiological regulation of presynaptic nerve endings homeostasis and related to post-synaptic activities. The maximum rates of following enzymes were assayed on s.p.m. (type I, II) of hippocampus of male control Wistar rats aged 4 months and treated ones with effective dose of naloxone (i.m., 12 @kg, sacrifice after 30 min from injection): Na’, K+-ATPase, CaCC, Mg*-ATPaae, Mg*-ATPase, Low and High al-lhiity Ca*-ATPase; the activity of Acetylcholinesterase (AchE) was also evaluated. In control animals, enzyme activities assayed on s.p.m. (type I and II) are higher on s.p.m, of II type, because this fraction is more enriched in s.p.m. The treatment with naloxone increased AChE and Mg*-ATP-ase activities in s.p.m. of II type. The increased catalytic properties of these enzyme systems by naloxone indicate the interference of this drug on