But be aware:
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Given to a non-psychotic patient, Pimozide can result in severe disabilities, both mental and physical. Loss of ability to lead a conversation is a common side effect. Due to that specific side effect, patients who have been wrongly given Pimozide cannot explain their need to stop taking the medication. Pimozide should be prescribed only after a complete medical examination and consensus between the patient and doctor.
This cant be for real, altough ap's make me completely retarded, i abrubtly stopped them as i got over benzo withdrawal as the severe retardation is too bad, so may be a bit hypomanic, but this shit comeone', obviously a joke.
As an aside:
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Pimozide Augmentation of Clozapine Inpatients with Schizophrenia and Schizoaffective Disorder Unresponsive to Clozapine Monotherapy
Joseph I Friedman,1,2,*Jean-Pierre Lindenmayer,3,4Frances Alcantara,5Stephanie Bowler,2Mohan Parak,3Leonard White,2Adel Iskander,3Michael Parrella,2David N Adler,6Nicholas D Tsopelas,7Wei-Yann Tsai,8Vladan Novakovick,1Philip D Harvey,9 and Kenneth L Davis1
Author information ► Article notes ► Copyright and License information ►
This article has been corrected. See Neuropsychopharmacology. 2011 May 14; 36(6): 1317.
This article has been corrected. See Neuropsychopharmacology. 2011 September 16; 36(10): 2150.
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Abstract
Despite its superior efficacy, clozapine is helpful in only a subset of patients with schizophrenia unresponsive to other antipsychotics. This lack of complete success has prompted the frequent use of various clozapine combination strategies despite a paucity of evidence from randomized controlled trials supporting their efficacy. Pimozide, a diphenylbutylpiperidine, possesses pharmacological and clinical properties distinct from other typical antipsychotics. An open-label trial of pimozide adjunctive treatment to clozapine provided promising pilot data in support of a larger controlled trial. Therefore, we conducted a double-blind, placebo-controlled, parallel-designed 12-week trial of pimozide adjunctive treatment added to ongoing optimal clozapine treatment in 53 patients with schizophrenia and schizoaffective disorder partially or completely unresponsive to clozapine monotherapy. An average dose of 6.48
mg/day of pimozide was found to be no better than placebo in combination with clozapine at reducing Positive and Negative Syndrome Scale total, positive, negative, and general psychopathology scores. There is no suggestion from this rigorously conducted trial to suggest that pimozide is an effective augmenting agent if an optimal clozapine trial is ineffective. However, given the lack of evidence to guide clinicians and patients when clozapine does not work well, more controlled trials of innovative strategies are warranted.
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Atypical properties of several classes of antipsychotic drugs on the basis of differential induction of Fos-like immunoreactivity in the rat brain.
Oka T, Hamamura T, Lee Y, Miyata S, Habara T, Endo S, Taoka H, Kuroda S.
Source
Department of Neuropsychiatry, Graduate School of Medicine and Dentistry, Okayama University, 2-5-1 Shikata-cho, Okayama 700-8558, Japan. toka@md.okayama-u.ac.jp
Abstract
Acute administration of typical and atypical antipsychotics has been reported to induce regionally distinct patterns of c-Fos expression in the rat forebrain. Furthermore, atypical index, the difference in the extent of increased Fos-like immunoreactivity (Fos-LI) in the nucleus accumbens (NAc) shell versus the dorsolateral striatum (DLSt), has been proposed to classify antipsychotics into typical or atypical antipsychotics. The present study was conducted to investigate the atypical properties of 24 antipsychotics that are used in Japan and blonanserin, a novel 5-HT2A and D2 receptor antagonist. We systematically examined the effects of the drugs on Fos-LI in the NAc and DLSt in the rat brain using immunohistochemistry and calculated the atypical index, comparing with those of haloperidol and clozapine. Floropipamide, oxypertine, nemonapride, pimozide and mosapramine, as well as clozapine, olanzapine, quetiapine and risperidone, showed high positive atypical index. Zotepine, perospirone, sulpiride, moperone, sultopride, thioridazine, carpipramine, clocapramine and blonanserin showed moderate ones. In contrast, fluphenazine, bromperidol, timiperone, spiperone, propericiazine, perphenazine, chlorpromazine and levomepromazine had negative atypical index like haloperidol. These results suggest that not only so-called atypical antipsychotics, but also several conventional drugs, possess atypical properties.
PMID: 15519367 [PubMed - indexed for MEDLINE]
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The effect of the antipsychotic drug mosapramine on the expression of Fos protein in the rat brain: comparison with haloperidol, clozapine and risperidone.
Fujimura M, Hashimoto K, Yamagami K.
Source
Tokyo Laboratories, Pharmaceutical Research Division, Welfide Corporation, LTD, Saitama, Japan. fujimura_masatake@welfide.co.jp
Abstract
In this study, we examined the effect of the acute p.o. administration of the antipsychotic drug mosapramine, as well as the antipsychotic drugsclozapine, haloperidol and risperidone, on the expression of Fos protein in the medial prefrontal cortex, nucleus accumbens and dorsolateral striatum of rat brain. The administration of mosapramine (1 or 3 mg/kg) significantly increased the number of Fos protein positive neurons in the medial prefrontal cortex, but not in the dorsolateral striatum. In addition, mosapramine (1, 3 or 10 mg/kg) produced a dose-dependent increase in the number of Fos protein positive neurons in the nucleus accumbens. The acute administration of 10 mg/kg of mosapramine significantly increased the number of Fos protein positive neurons in all brain regions. The acute administration of clozapine (30 mg/kg), similarly to mosapramine at lower doses (1 or 3 mg/kg), significantly increased the number of Fos protein positive neurons in the medial prefrontal cortex and nucleus accumbens, but not dorsolateral striatum. In contrast, haloperidol (0.3 mg/kg) significantly increased the number of Fos protein positive neurons in the nucleus accumbens and dorsolateral striatum, but not medial prefrontal cortex. The acute administration of risperidone (0.3 or 1 mg/kg) did not affect the number of Fos protein positive neurons in the medial prefrontal cortex, nucleus accumbens or dorsolateral striatum of rat brain, whereas a 3 mg/kg dose of risperidone significantly increased the number of Fos protein positive neurons in all brain regions. These results suggest that the ability of mosapramine to enhance expression of Fos protein in the medial prefrontal cortex may contribute to a clozapine-like profile with respect to actions on negative symptoms in schizophrenia. Furthermore, the lack of effect of low doses of mosapramine on Fos protein expression in the dorsolateral striatum, an area believed to play a role in movement, suggests that it may have a lower tendency to induce neurological side effects.
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nduction patterns of Fos-like immunoreactivity in the forebrain as predictors of atypical antipsychotic activity.
Robertson GS, Matsumura H, Fibiger HC.
Source
Department of Pharmacology, Faculty of Medicine, University of Ottawa, Ontario, Canada.
Abstract
Clozapine and haloperidol produce different induction patterns of c-fos expression in the forebrain, with haloperidol increasing Fos-like immunoreactivity (FLI) in the striatum, nucleus accumbens, lateral septal nucleus and clozapine producing such effects in the nucleus accumbens, prefrontal cortex and lateral septal nucleus. Accordingly, it was deemed possible that this approach may be useful in characterizing compounds with known or suggested antipsychotic actions. We therefore examined the effects of 17 compounds considered to be either typical, or atypical, antipsychotics on FLI in the prefrontal cortex, medial and dorsolateral striatum, nucleus accumbens and the lateral septal nucleus. Consistent with the hypothesis that the prefrontal cortex may be a target for some antipsychotic actions, FLI was elevated in this structure by clozapine, ICI 204,636, fluperlapine, RMI-81,582, remoxipride, molindone, melperone and tiospirone. Likewise, the ability of all of the compounds, except for risperidone, to enhance FLI in the lateral septal nucleus suggests that this limbic region also may be an important locus of antipsychotic action. All of the compounds examined elevated FLI in the nucleus accumbens and medial striatum, indicating that potential antipsychotic activity is predicted most consistently on this basis. Neuroleptics with a clearly documented liability for producing extrapyramidal side effects (EPS) such as chlorpromazine, fluphenazine, haloperidol, loxapine, metoclopramide and molindone elevated FLI in the dorsolateral striatum. In contrast, compounds unlikely to produce EPS such as clozapine, thioridazine, risperidone, remoxipride, fluperlapine, sulpiride, melperone and RMI-81,582 either failed to increase or produced minor elevations in FLI in the dorsolateral striatum.(ABSTRACT TRUNCATED AT 250 WORDS)
Then we got the benzamides.
Amusulpiride and sulpiride as GHB ligands, tiapride as a selective D1,D2, D3(weaker)D4 selective antagonist wich works for alcohol withdrawal induced delirium due to some unknown mechanism.
That clozapine is superior is far from suprising to me, its a gabab agonist and adding gabab agonists like phenibut to ap's that at first block amphetamine completely disinhibit the effects of amphetamine, gabab definatly massively modulates the effects of ap's. It doesnt matter if all da receptors are blocked.
We can learn some things from ap's, i still consider them garbage but this info can also be beneficial for treatment resistant ppl, oh yeah pimozide with clozapine id actually expect to fix me up pretty much, pimozide is a dri and cloz has the gabab agonism, only the 5HT2A antagonism is a bitch but i got reason to beleive 5HT4 agonism could prevent the retardation i get from it, not wanting to try tough
oh yeah
metoclopramide, D2 antagonist, 5HT4 agonist and partional 5HT3 antagonist, keep pramipexole ready it causes akathisia hell, also made me dystonic all day after i cant tolerate the shit much.
And:
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EXS. 2006;98:185-205.
Nicotinic-antipsychotic drug interactions and cognitive function.
Levin ED, Rezvani AH.
Source
Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, USA. edlevin@duke.edu
Abstract
In summary, neuronal nicotinic systems are important for a variety of aspects of cognitive function impacted by antipsychotic drugs. It has been demonstrated that antipsychotic drugs have memory and attentional impairing effects when given to unimpaired subjects. Nicotine can reduce some of these impairments, but antipsychotic drug administration can also attenuate nicotine effects. We have found that nicotinic agonists selective for alpha7 and alpha4beta2 receptor subtypes significantly improve learning and memory. Serotonergic actions of antipsychotic drugs may decrease efficacy of nicotinic co-treatments. When the antipsychotic drug clozapine and nicotine are administered to subjects with cognitive impairments caused by NMDA glutamate receptor blockade or hippocampal dysfunction they can significantly attenuate the attentional and memory impairments. Nicotine has been shown in our studies to reverse the memory impairment caused by acute clozapine-induced memory improvement. Acute risperidone and haloperidol has been shown to attenuate nicotine-induced memory improvement. We have determined the role of hippocampal alpha7 and alpha4beta2 nicotinic receptors in the neural basis of nicotinic antipsychotic interactions. Local acute and chronic hippocampal infusion of either nicotinic alpha7 or alpha4beta2 antagonists cause significant spatial working memory impairment. Chronic hippocampal nicotinic antagonist infusions have served as a model of persistent decreases in nicotinic receptor level seen in schizophrenia and Alzheimer's disease. Clozapine attenuated the memory deficit caused by chronic suppression of hippocampal alpha4beta2 receptors while the amnestic effects of clozapine were potentiated by chronic suppression of hippocampal alpha7 receptors. Nicotinic co-treatment may be a useful adjunct in the treatment of schizophrenia, to attenuate cognitive impairment of schizophrenia. Nicotine as well as selective nicotinic alpha7 and alpha4beta2 receptor agonists significantly improve working memory and attentional function. Nicotine treatment was found to be effective in attenuating the attentional and memory impairments caused by the psychototmimetic NMDA antagonist dizocilpine (MK-801), a model of the cognitive impairment of schizophrenia. Studies of the interactions of antipsychotic drugs with nicotinic agents provided quite useful information concerning possible co-treatment of people with schizophrenia with nicotinic therapy. Nicotine was found to significantly attenuate the memory impairments caused by the antipsychotic drugs clozapine and olanzapine. Interestingly, nicotine-induced cognitive improvement was significantly attenuated by the antipsychotic drug clozapine. One of the principal effects ofclozapine is to block 5HT2 receptors. Ketanserin a 5HT2 antagonist significantly attenuated nicotine-induced improvements in attention and memory. Thus it appears that antipsychotic drugs with actions blocking 5HT2 receptors may limit the efficacy of nicotinic co-treatments for cognitive enhancement.
Amisulpiride with lexapro, bromocriptine, amphetamine, nefiracetam, phenibut or baclofen and we got something replicating clozaping with pimozide (in theory atleast) or far better.