Posted by Chairman_MAO on September 16, 2005, at 10:46:12
In reply to Mom has to swich off Mellaril, whats closest ?, posted by linkadge on September 11, 2005, at 16:55:15
This drug seems to be forgotten, and I don't know why. Less likely to cause weight gain, seizures than other typicals. Has a receptor binding profile similar to quetiapine, IIRC.
1: Clin Neuropharmacol. 1996 Oct;19(5):444-50.
D-cycloserine adjuvant therapy to molindone in the treatment of schizophrenia.
Rosse RB, Fay-McCarthy M, Kendrick K, Davis RE, Deutsch SI.
Psychiatry Service, Department of Veterans Affairs Medical Center, Washington,
D.C. 20422, USA.This preliminary investigation examined the therapeutic efficacy of two doses of
oral D-cycloserine (5 and 15 mg p.o. b.i.d.) administered as an adjuvant to
molindone (150 mg p.o. q.d.) in the treatment of schizophrenia. D-Cycloserine is
an agonist at the N-methyl-D-aspartate (NMDA) subclass of glutamate receptor
complex. An NMDA agonist intervention was studied because of the
schizophreniform psychosis precipitated by phencyclidine (PCP), which is a
noncompetitive antagonist at the NMDA glutamate receptor. The PCP model of
schizophrenia is regarded as the most comprehensive pharmacological model of
this disorder. In this preliminary, placebo-controlled, double-blind,
parallel-group study, the measures of treatment efficacy were the Brief
Psychiatric Rating Scale, Schedule for the Assessment of Negative Symptoms, and
Clinical Global Impression Scale. The final scores for each item of the outcome
measures employed were based on the consensus of at least two trained raters who
were present during each rating interview. In the 13 subjects evaluated,
although the D-cycloserine was well tolerated, neither dose seemed to possess
adjuvant therapeutic efficacy. However, since another recent report of nine
patients with schizophrenia treated for 2 weeks with a slightly higher dose of
D-cycloserine (50 mg/day) described significant clinical and neuropsychological
improvement, further study of the adjuvant potential of slightly higher doses of
D-cycloserine seems warranted. Additionally, there might be a therapeutic window
for D-cycloserine dosing, as daily doses of 250 mg have been associated with
symptom worsening.Publication Types:
Clinical Trial
Randomized Controlled TrialMeSH Terms:
Administration, Oral
Adult
Aged
Antipsychotic Agents/therapeutic use*
Chemotherapy, Adjuvant
Cycloserine/therapeutic use*
Dose-Response Relationship, Drug
Drug Therapy, Combination
Humans
Middle Aged
Molindone/therapeutic use*
N-Methylaspartate/antagonists & inhibitors
Psychiatric Status Rating Scales
Schizophrenia/drug therapy*Substances:
Antipsychotic Agents
N-Methylaspartate
Cycloserine
MolindonePMID: 8889288 [PubMed - indexed for MEDLINE]
http://ajp.psychiatryonline.org/cgi/content/abstract/134/3/3021: Psychopharmacol Commun. 1975;1(4):349-58.
Effects of molindone on central dopaminergic neuronal activity and metabolism:
similarity to other neuroleptics.Bunney BS, Roth RH, Aghajanian GK.
The effect of molindone on the activity of dopaminergic (DA) neurons in the rat
midbrain and on DA metabolism in the striatum and olfactory tubercles was
studied using extracellular single unit recording and biochemical techniques
respectively. Molindone in low intravenous doses (0.4-0.8 mg/kg) was found to
reverse d-amphetamine and apomorphine induced depression of DA neurons and to
block apomorphine induced depression of these cells. Molindone was also found to
increase dopamine synthesis and dihydroxyphenylactic acid levels in the striatum
and olfacotry tubercles. In all of these respects molindone behaves identically
to most classical neuroleptics. However, unlike most antipsychotic drugs
previously tested, molindone failed to increase the baseline firing rate of DA
cells and blocked haloperidol induced increases in DA neuron activity.******* In this
regard molindone most closely resembles thioridazine [Mellaril] and clozapine. ********Possible
mechanisms of action of molindone are discussed based on these findings.MeSH Terms:
3,4-Dihydroxyphenylacetic Acid/metabolism
Animals
Corpus Striatum/metabolism
Dextroamphetamine/antagonists & inhibitors
Dopamine/metabolism
Dopamine/physiology*
Electric Stimulation
Electrophysiology
Indoles/pharmacology*
Male
Molindone/pharmacology*
Neurons/metabolism
Neurons/physiology*
Olfactory Pathways/metabolism
Rats
Research Support, U.S. Gov't, Non-P.H.S.
Tranquilizing Agents/pharmacology*Substances:
Indoles
Tranquilizing Agents
3,4-Dihydroxyphenylacetic Acid
Dopamine
Dextroamphetamine
MolindonePMID: 1224004 [PubMed - indexed for MEDLINE]
1: Mol Psychiatry. 1998 Mar;3(2):123-34.
Comment in:
Mol Psychiatry. 1998 Mar;3(2):101-2.Antipsychotic drugs which elicit little or no parkinsonism bind more loosely
than dopamine to brain D2 receptors, yet occupy high levels of these receptors.Seeman P, Tallerico T.
Department of Pharmacology, University of Toronto, Canada.
This review addresses two questions. First, why does clozapine apparently occupy
low levels of dopamine D2 receptors in patients, in contrast to all other
antipsychotic drugs which occupy 70-80% of brain dopamine D2 receptors? Second,
what is the receptor basis of action of antipsychotic drugs which elicit low
levels of Parkinsonism? Antipsychotic doses of clozapine occupy between 0% and
50% of D2 receptors, as measured in patients by a variety of radioligands. It
has recently been found, however, that the percent occupancy of a receptor by a
drug depends on the radioligand used to measure that receptor. Based on this new
finding, this review concludes that clozapine clinically occupies high levels of
D2 receptors in the absence of any radioligand. This occupancy is estimated to
be of the order of 70-80% in the dopamine-rich region of the human striatum, and
even higher in the limbic D2-containing regions which are low in endogenous
synaptic dopamine. This conclusion arises from two different approaches. One
approach is to relate the reported clozapine occupancies in the human striatum
with the dissociation constants of the various radioligands at the D2 receptor.
This relation extrapolates to approximately 70-80% occupancy by clozapine when
clozapine competes with endogenous dopamine at the D2 receptor. The second
approach is to calculate the D2 occupancy of each antipsychotic drug, using the
average spinal fluid concentration and the correct dissociation constant of the
antipsychotic, thereby revealing that all antipsychotic drugs, including
clozapine, occupy approximately 70-80% of dopamine D2 receptors in the human
striatum, and possibly higher in the limbic regions. As determined by the new
dissociation constants, antipsychotic drugs which elicit Parkinsonism
(trifluperazine, chlorpromazine, raclopride, haloperidol, fluphenazine,
risperidone) bind more tightly than dopamine to D2, while those antipsychotic
drugs which elicit little or no Parkinsonism (melperone, seroquel, perlapine,
clozapine, remoxipride, molindone, sulpiride, olanzapine, sertindole) bind more
loosely than dopamine to D2 receptors. Compared to the tightly bound
antipsychotic drugs, the more loosely bound antipsychotics generally require
higher clinical doses, require fewer days for clinical adjustment, but may
dissociate from the D2 receptor more rapidly and could lead to clinical relapse
somewhat earlier than that found with the traditional tightly bound
antipsychotic drugs.Publication Types:
ReviewPMID: 9577836 [PubMed - indexed for MEDLINE]
A cochrane review said that it is no less likely to cause TD than other typicals, however given its receptor binding profile, I'd rather play roulette with moban than thioridazine.1: Schizophr Res. 1990 Oct-Dec;3(5-6):315-20.
A comparison of masking effects of haloperidol versus molindone in tardive
dyskinesia.Glazer WM, Hafez H.
Yale University School of Medicine, TD Clinic, New Haven, CT 06519.
An experimental method was utilized to compare the masking effects of two
neuroleptic agents--molindone and haloperidol--on 18 neuroleptic-treated
schizophrenic patients exhibiting operationally defined withdrawal-exacerbated
tardive dyskinesia. After a week on one of these two medications at
preestablished doses equivalent to that of the pre-study neuroleptic,
molindone-masked total AIMS scores by significantly less (12%) than haloperidol
(27%). Similarly, during a second week when the dose of these neuroleptics was
equivalent to 200% that of the pre-study dose, molindone masked the total AIMS
score significantly less (23%) as compared to haloperidol (53%). Several
interpretations of this finding are considered. This study demonstrates the
feasibility of a method that may offer a model for understanding pharmacological
differences among neuroleptic medications.Publication Types:
Clinical Trial
Randomized Controlled TrialPMID: 1980827 [PubMed - indexed for MEDLINE]
1: Can J Psychiatry. 1990 Apr;35(3):268-9.
Polydipsia and hyponatremia induced by multiple neuroleptics but not molindone.
Glusac E, Patel H, Josef NC, Yeragani VK.
Wayne State University, Detroit, Michigan.
A 37 year old patient with chronic schizophrenia developed polydipsia and
hyponatremia induced by several neuroleptics. We treated the patient
successfully with molindone. The etiology of polydipsia with hyponatremia is
discussed.Publication Types:
Case ReportsPMID: 1971192 [PubMed - indexed for MEDLINE]
1: J Clin Psychopharmacol. 1989 Aug;9(4):268-76.
Molindone hydrochloride: a review of laboratory and clinical findings.
Owen RR Jr, Cole JO.
Clinical Neuroscience Branch, National Institute of Mental Health, Bethesda,
Maryland.Molindone hydrochloride, a dihydroindolone neuroleptic, is structurally distinct
from other classes of neuroleptics. Molindone exhibits many similarities to
other neuroleptics, including dopamine receptor blockade, antipsychotic
efficacy, and extrapyramidal side effects. Despite these similarities, molindone
also has atypical properties and inhibits the enzyme monoamine oxidase in vitro
and in vivo. Several studies have shown that molindone causes less dopamine
receptor supersensitivity than other neuroleptics and thus may be less likely to
cause tardive dyskinesia. It also appears to have a greater effect on mesolimbic
and mesocortical dopamine neurons than on those in the nigrostriatal dopamine
system. Clinically, molindone has a tendency to cause weight loss and may have
less effect on seizure threshold than conventional antipsychotic agents. The
authors review the laboratory and clinical data on molindone and discuss the
relevance of atypical research findings to the clinical characteristics of this
antipsychotic agent.Publication Types:
Review
Review, TutorialPMID: 2671060 [PubMed - indexed for MEDLINE]
poster:Chairman_MAO
thread:553834
URL: http://www.dr-bob.org/babble/20050914/msgs/555640.html