P
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f Introduction
Pimozide has traditionally been the drug of choice for u in patients with delusions of parasitosis [Hamann and Avnstorp,1982; Munro, 1988; Lee et al., 2003]. Its mechanism of action is
well known as a highly lective dopamine D 2antagonist with
relative lack of noradrenergic and rotonergic blockade [Manschreck, 2000]. However, it has been suggested that pi-mozide’s unique efficacy for delusions of parasitosis derives from the fact that it, unlike other neuroleptics in common u,
contest
Pimozide: The Opiate Antagonist Hypothesis and U in Delusions of Parasitosis
M. Lee a J. Koo b
a Rosalind Franklin University of Medicine and Science, Chicago, IL,
cityhunter
b Department of Dermatology, University of California, San Francisco, CA, USA
Key Words
Pimozide · Opioid-related disorders · Receptors, Opioi ·Substance withdrawal syndrome · Hypochondriasis
Summary
Introduction:Pimozide, a neuroleptic ag ent frequently ud in the treatment of delusions of parasitosis, has been thoug ht to have a better therapeutic efficacy for delusions of parasitosis than other antipsychotic agents becau of its dual effect of blocking opiate as well as dopamine transmission. If so, this may prent a prob-lem in patients who are dependent on opiates, who would undergo withdrawal when given a strong opiate antagonist such as naloxone. Methods and Results:A lit-erature arch was conducted and evidence was found to alleviate the fears that pimozide would precipitate opiate withdrawal. Although no reports of human stud-ies were found, veral studies have shown that with-drawal is not obrved when giving pimozide to opiate-depend
ent animals. Moreover, the bas for the mecha-nism of pimozide as an opiate antagonist and for the role of opiate neurotransmission in delusions of parasitosis were found to be still controversial.
soforthSchlüslwörter
Pimozid · Opioid-abhängige Störungen · Rezeptoren,Opioid · Entzugssyndrom · Hypochondrie
Zusammenfassung
Pimozid: Die Opiat-Antagonist-Hypothe und der Einsatz bei Dermatozoenwahn
Einleitung:Pimozid ist ein Neuroleptikum, das oft zur Behandlung von Dermatozoenwahn eingetzt wird. Auf-grund iner doppelten Wirkungswei auf die Blockie-rung von Opiaten einerits und die Dopamintransmis-sion andererits wird es für therapeutisch wirksamer er-achtet als andere Antipsychotika. Allerdings könnte dies bei Patienten mit Opiatabhäng ig keit zu Problemen füh-ren, da die unter Entzug kämen, wenn ihnen ein star-ker Opiat-Antag onist wie Naloxon g eg eben würde.Methode und Ergebnis:Wir haben eine Literaturre-cherche durchg eführt und Hinwei g efunden, welche die Befürchtung, dass Pimozid einen Opiatentzug auslö-n könnte, zerstreuen. Zwar haben wir keine Studien an Menschen g efunden, mehrere Untersuchung en haben jedoch gez
eigt, dass kein Entzug beobachtbar war, wenn opiatabhäng ig en Tieren Pimozid g eg eben wurde. Dar-über hinaus fanden wir, dass die Wirkmechanismen von Pimozid als Opiatantag onist und für die Rolle bei der Neurotransmission von Opiaten bei Dermatozoenwahn immer noch strittig sind.
Original Article ·Originalarbeit
Dermatol Psychosom 2004;5:■■■■
Melvin Lee
4645 Whitewood Ave
Long Beach, CA 90808, USA Tel. +1 312 543–0205, Fax
E-Mail melvin.salindfranklin.edu
© 2004 S. Karger GmbH, Freiburg
Accessible online at:
/dps Fax +49 761 4 52 07 14
E-mail Information@Karger.de
P
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f may also block opiate receptors [Opler and Feinberg, 1991;Driscoll et al., 1993; Tennyson and Levine, 2001]. This later mechanism is of concern in chronic opiate urs who develop delusions of parasitosis. One might wonder whether to avoid pimozide in the patients to prevent the risk of opiate with-drawal. This is also particularly relevant becau one impor-tant differential diagnosis of delusions of parasitosis especially in younger patients is substance abu, includin
hurt的意思
g the u of co-caine, amphetamines, narcotics, or a mixture of the drugs.This article is an update on the evidence regarding the hy-pothesis that pimozide may be an opiate receptor antagonist and whether pimozide is safe in opiate-dependent patients.
Methods
Searches for relevant articles were conducted in electronic databas in-cluding PubMed 1951–2004, MEDLINE (National Library of Medicine)1966–2004, OLDMEDLINE (National Library of Medicine) 1951–1965,and the Cochrane Controlled Trials Register. The arch terms included various combinations of pimozide and relevant terms indicating the opiate antagonist mechanism or opiate withdrawal, or the u of pimozide in pa-tients with delusions of parasitosis (pimozide, opiate, withdrawal, para-sitosis, infestation, delusion, naloxone, naltrexone, pruritus). The abstracts were evaluated and the full articles of possibly relevant studies and ca reports were read. Additional papers were obtained from the references cited in pertinent articles. Several dermatology, psychiatry, and pharma-cology textbooks were also consulted for journal references (textbooks included Kaplan and Sadock’s Comprehensive Textbook of Psychiatry, 7th ed; Kaplan and Sadock’s Synopsis of Psychiatry, 9th ed; Fitzpatrick’s Der-matology in General Medicine, 4th ed and 5th ed; Dermatology by Bolog-nia et al; Advanced Dermatologic Therapy I ; and Goodman and Gilman’s The Pharmacolo
gical Basis of Therapeutics, 9th ed). I n total,over 1,000 abstracts were evaluated and over 100 full articles were read.
Results
Charalampous and Askew [1974] were the first group to study the interaction between pimozide and the opiate receptor.They did this by testing the ability of pimozide to inhibit the binding of tritiated-naloxone to the opiate receptor. Compar-ing pimozide with controls, they found that pimozide did not significantly affect the binding of naloxone. Conquently,they concluded that pimozide does not have a significant in-teraction with the opiate receptor.
Cree et al. [1976] did similar experiments, but instead they found that the strength of naloxone binding inhibition by pi-mozide was comparable to opiates including morphine and propoxyphene. Previous experiments by Pert and Snyder [1975] demonstrated that the known opiate agonists were much less able to inhibit the binding of naloxone in the pres-ence of sodium while known opiate antagonists tested did not lo inhibitory potency. Extrapolating from this work, Cree et al. obrved that pimozide lost some ability to inhibit the binding of naloxone when sodium was added to the homo-genate, but its inhibitory potency did not decrea nearly as
much as that of known opiates. Thus they suggested that pimozide may be an opiate antagonist.
No other laboratory experiments were found to further clarify the interaction between pimozide and the opiate receptor, but a few groups have published hypothes bad on the possible opiate receptor antagonist mechanism of pimozide. Johnson and Anton [1983] were the first to speculate that opiate neu-rotransmission may play a role in delusions of parasitosis.Their reasoning was that opiate antagonists emed to have an effect on the pruritus of biliary cirrhosis. Since pimozide had been established as a drug of choice in delusions of parasitosis and possibly interacts with the opiate receptor, they hypothe-sized that opiate neurotransmission may also play a role in delusions of parasitosis.
Although the effect of pimozide on opiate receptors has not been proven, one group published a ca report that emed to correlate with the hypothesis that opiate neurotransmission may play a role in delusions of parasitosis. I n that paper,Botschev and Muller [1991] described a patient with delusions of parasitosis who condition worned when fentanyl (an opiate agonist) was given, and improved with naloxone or nal-trexone (opiate antagonists).
Several groups have ud pimozide in opiate dependence models, though all the studies to date h
ave been in rats,mice, and hamsters. None of the studies have shown that pimozide produces a withdrawal effect when given to opiate-dependent rats, mice, or hamsters [Cox et al., 1975, 1976; Ary et al., 1977; Neiwander and Bardo, 1987; Schnur et al., 1994;Rezayat et al., 1997; el-Kadi and Sharif, 1998]. Moreover,when pimozide was given before naloxone to opiate-depen-dent rats or hamsters, many of the studies actually demon-strate attenuation of many signs of withdrawal (i.e. jumping,wet dog shakes, burrows, body weight loss, withdrawal hy-pothermia, and thermoregulatory behavioral changes). The effects were found to be consistent with other neuroleptics tested, so it was thought that the blockade of dopamine neu-rotransmission is responsible, rather than an effect on opiate neurotransmission.
Discussion
The clinical relevance of pimozide on opiate receptor antago-nism is still controversial. Only one of two studies was able to
show a possible interaction between pimozide and opiate re-ceptors [Charalampous and Askew, 1974; Cree et al., 1976].Moreover, the single report suggesting the possibility that pi-mozide may be an opiate antagonist evaluated this indirectly;no direct asssment of the effect of pimozide on opiate re-ceptor function in vitro has ever been published.
dilemmaSeveral animal studies have, in fact, shown that pimozide has little interaction (if any at all) with the opiate receptor [Cox et al., 1975, 1976; Ary et al., 1977; Neiwander and Bardo, 1987;Schnur et al., 1994; Rezayat et al., 1997; el-Kadi and Sharif,
Dermatol Psychosom 2004;5:■■–■■
Pimozide: The Opiate Antagonist Hypothesis and U in Delusions of Parasitosis
3
P
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f 1998]. After the administration of pimozide to opiate-depen-dent rodents, none of the studies’ authors obrved an opiate withdrawal. Rather, pimozide actually was shown to decrea the signs of withdrawal when given before naloxone.
Although the data shows that pimozide does not cau opiate withdrawal in animal studies, this data has not been confirmed in human trials. No reports described the u of pimozide in opiate-dependent patients, nor were there papers describing the u of pimozide and opiates together in human subjects.However, neuroleptics in general have by themlves been re-ported to alleviate symptoms of opiate withdrawal in humans [Karkalas and Lal, 1973].
It is also still unknown whether the possible effect of pimozide on opiate receptors plays a role in the treatment of delusions of parasitosis. The hypothesis that opiate receptors are in-volved in delusions of parasitosis was extrapolated from work on the pruritus of biliary cirrhosis [Johnson and Anton, 1983].However, the two conditions may have little in common other
than pruritus, and there is a psychotic component in delusions of parasitosis. Moreover, only a single ca report has been published which implicates the possibility that opiate neuro-transmission may be involved in delusions of parasitosis [Botschev and Muller, 1991]. The results of this ca report have not been confirmed by other studies.
Conclusion
思维导图培训The in vitro study showing that pimozide has some properties similar to opiate antagonists has been
well recognized. How-ever, definitive proof to demonstrate that pimozide blocks the opiate receptor in vitro or in vivo is still lacking. Other studies have also shown that pimozide does not cau withdrawal in opiate-dependent animals. Thus, the available limited evi-dence shows that pimozide may be safe to u with opiate-dependent patients in this regard.
cle4Dermatol Psychosom 2004;5:■■–■■Lee/Koo
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