Use Of Pimozide Research Articles

Pimozide as an effective treatment for obsessive symptoms related to physical discomfort in the context of somatoform symptomatology.

IntroductionThe patient was a 34-year-old male admitted to the psychiatric inpatient unit for high anxiety and suicide ideation due to severe toothache.ObjectivesTo show how the antipsychotic pimozide can be an effective option for the treatment of anxiety and obsessive symptoms around physical complaints within the spectrum of somatoform disordersMethodsCase report and literature reviewResults The patient comes to the emergency room with high anxiety and active self-harming ideation. He reports that for months he has been experiencing mouth pain that is becoming more and more intense. He has seen multiple professionals without finding a cause that justifies the pain. In the past she has a history of multiple ailments (knee, abdominal pain…). He is being treated with sertraline 150, clonazepam 3 mg per day and olanzapine 5 mg at night. During admission, treatment with pimozide up to 4 mg per day was started. The patient is progressively less distressed and with more distance from the ideas about pain, being able to carry out more activities during the day. There is remission of suicidal ideationConclusionsThere is evidence in the literature that the use of pimozide was effective in different psychotic disorders. It has been seen to reduce the intensity of symptoms in cases of delusional disorders with delirum of somatic type or those such as delusions by parasitization. The use of pimozide has also been effective in the treatment of complex tic disorder. In this case it is effective and could be explained by the close relationship of osbsesive symptoms with psychotic symptoms.Disclosure of InterestNone Declared

The enhanced antitumour response of pimozide combined with the IDO inhibitor L‑MT in melanoma.

Melanoma is one of the most fatal and therapy-resistant types of cancer; therefore, identifying novel therapeutic candidates to improve patient survival is an ongoing effort. Previous studies have revealed that pimozide is not sufficient to treat melanoma; therefore, enhancing the treatment is necessary. Indoleamine 2, 3-dioxygenase (IDO) is an immunosuppressive, intracellular rate-limiting enzyme, which contributes to immune tolerance in various tumours, including melanoma, and inhibition of IDO may be considered a novel therapeutic strategy when combined with pimozide. The present study aimed to assess the antitumour activities of pimozide in vitro, and to investigate the effects of pimozide combined with L-methyl-tryptophan (L-MT) in vivo. For in vitro analyses, the B16 melanoma cell line was used. Cell cytotoxicity assay, cell viability assay, wound-healing assay and western blotting were conducted to analyse the effects of pimozide on B16 cells. Furthermore, B16 cell-bearing mice were established as the animal model. Haematoxylin and eosin staining, immunohistochemistry, terminal deoxynucleotidyl transferase dUTP nick end-labelling staining, western blotting and flow cytometry were performed to determine the effects of monotherapy and pimozide and L-MT cotreatment on melanoma. The results demonstrated that pimozide exhibited potent antitumour activity via the regulation of proliferation, apoptosis and migration. Furthermore, the antitumour effects of pimozide were enhanced when combined with L-MT, not only via regulation of proliferation, apoptosis and migration, but also via immune modulation. Notably, pimozide may regulate tumour immunity through inhibiting the activities of signal transducer and activator of transcription (Stat)3 and Stat5. In conclusion, the present study proposed the use of pimozide in combination with the IDO inhibitor, L-MT, as a potential novel therapeutic strategy for the treatment of melanoma.

Canadian Guidelines for the Evidence-Based Treatment of Tic Disorders: Pharmacotherapy

This article seeks to provide the practising clinician with guidance on the pharmacological management of tic disorders in children and adults. We performed a systematic review of the literature on the treatment of tic disorders. A multi-institutional group of 14 experts in psychiatry, child psychiatry, neurology, pediatrics, and psychology engaged in a consensus meeting. The evidence was presented and discussed, and nominal group techniques were employed to arrive at consensus on recommendations. A strong recommendation is made when the benefits of treatment clearly outweigh the risks and burdens, and can apply to most patients in most circumstances without reservation. With a weak recommendation, the benefits, risks, and burdens are more closely balanced, and the best action may differ depending on the circumstances. Based on these principles, weak recommendations were made for the use of pimozide, haloperidol, fluphenazine, metoclopramide (children only), risperidone, aripiprazole, olanzapine, quetiapine, ziprasidone, topiramate, baclofen (children only), botulinum toxin injections, tetrabenazine, and cannabinoids (adults only). Strong recommendations were made for the use of clonidine and guanfacine (children only). While the evidence supports the efficacy of many of the antipsychotics for the treatment of tics, the high rates of side effects associated with these medications resulted in only weak recommendations for these drugs. In situations where tics are not severe or disabling, the use of a medication with only a weak recommendation is not warranted. However, when tics are more distressing and interfering, the need for tic suppression to improve quality of life is stronger, and patients and clinicians may be more willing to accept the risks of pharmacotherapy.

Complete Atrioventricular Block in a Young Schizophrenia Patient

Back to table of contents Previous article Next article LETTERFull AccessComplete Atrioventricular Block in a Young Schizophrenia PatientFilipi Costa Dias M.D.,Hugo Canos Prais M.D., M.Sc.,Rose M F Lisboa da Silva M.D., Ph.D.,Humberto Correa M.D., Ph.D.,Filipi Costa Dias M.D.Search for more papers by this author,Hugo Canos Prais M.D., M.Sc.Search for more papers by this author,Rose M F Lisboa da Silva M.D., Ph.D.Search for more papers by this author,Humberto Correa M.D., Ph.D.Search for more papers by this author,Published Online:1 Apr 2010https://doi.org/10.1176/jnp.2010.22.2.247.e30AboutSectionsView articlePDFView EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail View articleTo the Editor: It is widely known that psychiatric patients have higher rates of death from several causes, including cardiovascular disease, especially among those with schizophrenia. 1 A wide number of factors may contribute to this increased risk, including the use of psychotropic agents with cardiovascular adverse effects. Soon after their discovery, antipsychotics were related to sudden death. Traditionally, the main effect of antipsychotics takes place on the heart conduction system and the QT interval. 2 Complete atrioventricular block is not routinely associated with the use of antipsychotics, and, to our concern, there has been only one report of the development of atrioventricular block concurrent with the use of antipsychotics. 3We hereby present a case report of a 20-year-old man with schizophrenia who developed complete atrioventricular block during the use of antipsychotics while he was under inpatient treatment at Galba Velloso Hospital in Belo Horizonte, Minas Gerais, Brazil. He had been under irregular psychiatric treatment since he was 16, using lithium carbonate, carbamazepine, and risperidone, and despite the treatment there had been no improvement in his state. In a psychiatric forensic exam he was diagnosed as having disorganized schizophrenia or hebephrenia. There was no medical history of clinical comorbidities other than a report of alcohol abuse since the age of Initially he was prescribed haloperidol (10 mg/day) and lorazepam (2 mg/night); carbamazepine (800 mg/day) was gradually added to his regimen in an attempt to control the impulsivity and disorganized behavior. Since there was no improvement after 18 days of this treatment, we substituted haloperidol with pimozide, 4 mg t.i.d., before trying an atypical antipsychotic. Two days after this change, the patient presented syncope with heart rate of 20 bpm and blood pressure of 140 × 90 mm Hg. A bedside ECG revealed signs of complete atrioventricular block, high amplitude QRS complexes, and a QTc of 560 ms ( Figure 1 ). He was transferred to the Hospital of Clinics of the Federal University of Minas Gerais, where a temporary transvenous pacemaker was used in an attempt to correct the arrhythmia. Although drugs were washed out, there was persistent conduction disturbance, which led to the implantation of a permanent pacemaker. Biochemical exams revealed no abnormalities in the electrolytes, liver, or kidney functions, and a chest radiography showed an increased cardio-thoracic index. Thyroid function and trypanosome serology studies had normal values. A cardiologic examination confirmed the diagnosis of asymptomatic heart failure probably due to alcoholic cardiomyopathy. An echocardiogram showed dilated cardiomyopathy with an ejection fraction of 39%. The patient is currently being treated with olanzapine (20 mg/day) and lithium carbonate (1,200 mg/day), resulting in good control of psychotic symptoms and disorganized behavior; he has had no other cardiovascular events since. FIGURE 1. Bedside ECG Showing Complete Atrioventricular Block, Pathological Q-Waves, and High-Amplitude QRS ComplexesThis is, up to the moment, the first case report of the development of an atrioventricular block attributable to the use of pimozide, considering that the patient had presented no cardiovascular event when he previously used carbamazepine. This report indicates the importance of clinical monitoring of psychiatric patients, in an attempt to prevent sudden events that could have lethal consequences.Postgraduation Program of the Department of Internal Medicine, Federal University of Minas Gerais, Belo Horizonte, BrazilMental Health Section of the Department of Medical Sciences, Federal University of Ouro Preto, Ouro Preto, BrazilDepartment of Internal Medicine, Federal University of Minas Gerais, Belo Horizonte, BrazilDepartment of Mental Health, Federal University of Minas Gerais, Belo Horizonte, Brazil

Complete Atrioventricular Block in a Young Schizophrenia Patient

Back to table of contents Previous article Next article LETTERFull AccessComplete Atrioventricular Block in a Young Schizophrenia PatientFilipi Costa Dias M.D.,Hugo Canos Prais M.D., M.Sc.,Rose M F Lisboa da Silva M.D., Ph.D.,Humberto Correa M.D., Ph.D.,Filipi Costa Dias M.D.Search for more papers by this author,Hugo Canos Prais M.D., M.Sc.Search for more papers by this author,Rose M F Lisboa da Silva M.D., Ph.D.Search for more papers by this author,Humberto Correa M.D., Ph.D.Search for more papers by this author,Published Online:1 Apr 2010https://doi.org/10.1176/jnp.2010.22.2.247.e30AboutSectionsView articlePDFView EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail View articleTo the Editor: It is widely known that psychiatric patients have higher rates of death from several causes, including cardiovascular disease, especially among those with schizophrenia. 1 A wide number of factors may contribute to this increased risk, including the use of psychotropic agents with cardiovascular adverse effects. Soon after their discovery, antipsychotics were related to sudden death. Traditionally, the main effect of antipsychotics takes place on the heart conduction system and the QT interval. 2 Complete atrioventricular block is not routinely associated with the use of antipsychotics, and, to our concern, there has been only one report of the development of atrioventricular block concurrent with the use of antipsychotics. 3We hereby present a case report of a 20-year-old man with schizophrenia who developed complete atrioventricular block during the use of antipsychotics while he was under inpatient treatment at Galba Velloso Hospital in Belo Horizonte, Minas Gerais, Brazil. He had been under irregular psychiatric treatment since he was 16, using lithium carbonate, carbamazepine, and risperidone, and despite the treatment there had been no improvement in his state. In a psychiatric forensic exam he was diagnosed as having disorganized schizophrenia or hebephrenia. There was no medical history of clinical comorbidities other than a report of alcohol abuse since the age of Initially he was prescribed haloperidol (10 mg/day) and lorazepam (2 mg/night); carbamazepine (800 mg/day) was gradually added to his regimen in an attempt to control the impulsivity and disorganized behavior. Since there was no improvement after 18 days of this treatment, we substituted haloperidol with pimozide, 4 mg t.i.d., before trying an atypical antipsychotic. Two days after this change, the patient presented syncope with heart rate of 20 bpm and blood pressure of 140 × 90 mm Hg. A bedside ECG revealed signs of complete atrioventricular block, high amplitude QRS complexes, and a QTc of 560 ms ( Figure 1 ). He was transferred to the Hospital of Clinics of the Federal University of Minas Gerais, where a temporary transvenous pacemaker was used in an attempt to correct the arrhythmia. Although drugs were washed out, there was persistent conduction disturbance, which led to the implantation of a permanent pacemaker. Biochemical exams revealed no abnormalities in the electrolytes, liver, or kidney functions, and a chest radiography showed an increased cardio-thoracic index. Thyroid function and trypanosome serology studies had normal values. A cardiologic examination confirmed the diagnosis of asymptomatic heart failure probably due to alcoholic cardiomyopathy. An echocardiogram showed dilated cardiomyopathy with an ejection fraction of 39%. The patient is currently being treated with olanzapine (20 mg/day) and lithium carbonate (1,200 mg/day), resulting in good control of psychotic symptoms and disorganized behavior; he has had no other cardiovascular events since. FIGURE 1. Bedside ECG Showing Complete Atrioventricular Block, Pathological Q-Waves, and High-Amplitude QRS ComplexesThis is, up to the moment, the first case report of the development of an atrioventricular block attributable to the use of pimozide, considering that the patient had presented no cardiovascular event when he previously used carbamazepine. This report indicates the importance of clinical monitoring of psychiatric patients, in an attempt to prevent sudden events that could have lethal consequences.Postgraduation Program of the Department of Internal Medicine, Federal University of Minas Gerais, Belo Horizonte, BrazilMental Health Section of the Department of Medical Sciences, Federal University of Ouro Preto, Ouro Preto, BrazilDepartment of Internal Medicine, Federal University of Minas Gerais, Belo Horizonte, BrazilDepartment of Mental Health, Federal University of Minas Gerais, Belo Horizonte, Brazil

Delusions of parasitosis

Delusions of parasitosis is a rare psychiatric disorder in which the patient has a fixed, false belief that he or she is infested by parasites. Even though it is a psychiatric disorder, these patients usually present to a dermatologist because they are convinced that they have a dermatologic problem. Patients with delusions of parasitosis generally reject psychiatric referral. The traditional treatment of choice for delusions of parasitosis is the antipsychotic medication pimozide (Orap, Gate Pharmaceuticals, Philadelphia, PA). The use of pimozide has been limited by its adverse effects, most notably extrapyramidal adverse effects. There is now an emerging role for atypical antipsychotics with a safer adverse effect profile in the treatment of delusions of parasitosis. However, the most challenging aspect of managing these patients may be the challenge of establishing rapport in the face of unshakable delusional ideation.

Pimozide Inhibits STAT5 Signaling in Chronic Myelogenous Leukemia and Reduces the Viability of Both Imatinib Sensitive and Imatinib Resistant Cells.

Chronic myelogenous leukemia (CML) is characterized by the BCR/ABL fusion tyrosine kinase which mediates its oncogenic effects in part through constitutive activation of the transcription factor STAT5. BCR/ABL can be inhibited by several kinase inhibitors, including imatinib, which leads to apoptosis of the cells. However, the development of resistance to these agents, most commonly mediated through point mutations in the kinase, is an increasing problem. Since STAT5 is a critical mediator of the effects of BCR/ABL, the development of drugs inhibiting this transcription factor holds promise as an independent means to inhibit BCR/ABL-transformed cells. Therefore, we developed a high throughput cell-based screen to identify drugs that specifically inhibit the transcriptional function of STAT proteins. To accelerate the introduction of active agents into clinical trials, we have focused on drugs that are approved for use, or are otherwise known to be safe, in humans. Using this approach, we have identified pimozide, a neuroleptic drug, as an inhibitor of STAT5. Pimozide decreases STAT5 phosphorylation in CML cells but, in contrast to imatinib, it does not inhibit BCR/ABL kinase activity. Furthermore, pimozide decreases expression of STAT5 target genes in these cells. Consistent with the known role of STAT5 in promoting the survival and proliferation of BCR/ABL-transformed cells, pimozide induces apoptosis in the K562 CML cell line. At similar concentrations, pimozide induces little toxicity in peripheral blood mononuclear cells from normal donors. Given the clinical importance of point mutations in BCR/ABL in the development of resistance to tyrosine kinase inhibitors, we evaluated the effects of pimozide in Ba/f3 cells reconstituted with wildtype BCR/ABL or BCR/ABL containing a T315I mutation, which is highly resistant to current kinase inhibitors. Pimozide reduces the viability of both cell types with similar dose response, providing further support to the hypothesis that this drug works by a mechanism distinct from imatinib. Given this, we considered the possibility that the combination of pimozide and imatinib might be more effective than either drug alone. Treatment of KU812 CML cells with low concentrations of both pimozide and imatinib induced greater loss of viability than either drug alone, with characteristics consistent with pharmacological synergy. In addition, combination treatment with pimozide and imatinib induces a greater level of apoptosis in CML cells than either drug alone. In conclusion, we have identified pimozide as a STAT5 inhibitor that is effective at reducing the viability of CML cells, including those resistant to imatinib. This suggests that the identification of inhibitors of STAT transcription factors may be a promising method for developing new anti-cancer therapies. In addition, the use of pimozide alone or in conjunction with kinase inhibitors may be an important new strategy for the treatment of CML or other diseases characterized by constitutive STAT activation.

Effect of gonadotropin-releasing hormone analogue (GnRHa) and pimozide on plasma levels of sex steroids and ovarian development in sea bass ( Dicentrarchus labrax L.)

To synchronise and advance spawning, European sea bass females in late vitellogenesis were treated with two i.p. injections of GnRH analogue alone (5 and 20 μg/kg BW) given 12 h apart, or combined with pimozide (PIM) (10 mg/kg BW) either in the first or second injection. Saline-injected and untreated females were used as controls. Administration of GnRHa alone or combined with PIM accelerated the final oocyte maturation (FOM) and induced spawning. However, 48 h after the second injection the size of oocytes and the percentage of oocytes in GVBD stage were lower in the PIM-treated females. The number of eggs spawned was highest in the group that received GnRHa alone and lowest in the group that received PIM in the second injection. Plasma levels of 17β-oestradiol (E2) increased sharply at 12 h after the first injection of GnRHa alone or combined with PIM, decreasing after a second injection of GnRHa alone. However, the plasma E2 decreases was much slower in females that received the PIM in the first injection. Females that received PIM in the second injection still showed elevated plasma E2 during a longer period. Plasma testosterone (T) increase was parallel to the plasma E2 decrease and peaked earlier in the group that received GnRHa alone in both injections. Low and nonsignificant changes of 17α,20β-dihydroxy-4-pregen-3-one (17,20β-P) were observed in plasma during the time that the animals were sampled. The results demonstrate that the use of PIM does not improve the GnRHa treatment and the use of GnRHa alone during the last stages of vitellogenesis is enough to induce FOM in the European sea bass.

Effect of clarithromycin on the pharmacokinetics and pharmacodynamics of pimozide in healthy poor and extensive metabolizers of cytochrome P450 2D6 (CYP2D6)

The use of pimozide is associated with prolongation of the QT interval and fatal ventricular arrhythmia. We recently reported 2 fatal cases in patients taking pimozide and clarithromycin and we have shown that clarithromycin inhibits CYP3A-mediated metabolism of pimozide in vitro. In this study, we examined the effect of clarithromycin on pimozide pharmacokinetics and QT interval changes in a total of 12 healthy subjects (7 men and 5 women), documented as extensive metabolizers or poor metabolizers of CYP2D6. In a randomized, double-blind placebo-controlled crossover design, subjects were given a single 6-mg oral dose of pimozide after 5 days of treatment with clarithromycin (500 mg twice a day) or a placebo pill. Blood samples were obtained before and for 96 hours after pimozide administration, and plasma pimozide and clarithromycin concentrations were measured by HPLC. Electrocardiograms for the analysis of the QTc intervals were recorded immediately before each blood sample. Pimozide significantly lengthened QTc interval in the first 20 hours in both the placebo-treated groups (delta QTcmax = 13.3 +/- 5.3 ms; P = .003) and clarithromycin-treated groups (delta QTcmax = 15.7 +/- 9.5 ms; P = .005) compared with baseline values. This is consistent with an effect of the parent drug. Clarithromycin caused a significant increase in the peak plasma concentration (P = .015), terminal elimination half-life (P = .003), and area under the plasma concentration-time curve (P = .024) and a decrease in the clearance (P = .029) of pimozide. Mean QTcmax observed within 20 hours of pimozide administration was significantly greater in the clarithromycin-treated group (23.8 +/- 12.2 ms; P = .0397) than in the placebo-treated group (16.8 +/- 6 ms). There was no significant effect of CYP2D6 or gender on the pharmacokinetics or pharmacodynamics of pimozide. A single 6-mg oral dose of pimozide resulted in measurable QT interval changes. Clarithromycin inhibited CYP3A-mediated pimozide metabolism and the resulting elevation in plasma concentrations may increase the risk of pimozide cardiotoxicity.

A Fatality Involving Moclobemide, Sertraline, and Pimozide

Abstract A case is described involving a suspected fatal interaction between moclobemide and sertraline, in combination with the use of pimozide.

DELUSIONS OF PARASITOSIS AND OTHER FORMS OF MONOSYMPTOMATIC HYPOCHONDRIACAL PSYCHOSIS: General Discussion and Case Illustrations

In this article, the epidemiology and differential diagnosis of monosymptomatic hypochondriacal psychosis are discussed in detail. The use of pimozide is also discussed and illustrated with case reports. Delusional patients are some of the most challenging cases based in dermatologic practice. This challenge is so much easier to meet if one knows how to approach these patients and feels comfortable in the use of pimozide.

Pimozide as a replacement for maintenance therapy in chronic schizophrenia.

An open 12-week study was carried out to investigate the use of pimozide (12 mg once daily) as a replacement for antipsychotic maintenance therapy in 30 chronic schizophrenics who had responded poorly to previous neuroleptic monotherapy or polytherapy. After 8 weeks of treatment with pimozide, all 18 symptoms of the Brief Psychiatric Rating Scale were improved from previous treatment values. These differences were statistically significant for conceptual disorganization, depressive mood, hostility and motor retardation. Eleven patients who clearly responded well during the trial and consequently continued pimozide monotherapy were judged, 1 year later, to be functioning as well, or better, than with pre-trial drug treatment.

Effects of pimozide on the response of smooth muscle to non-dopamine agonists and calcium

Pimozide inhibits acetylcholine and histamine-induced contractions of the isolated guinea-pig ileum and noradrenaline-induced contractions of the isolated rat vas deferens in a non-competitive manner. In order to explore the nature of this inhibitory effect, we investigated pimozide's effects on calcium-induced contractions of depolarized guinea-pig ileum. In this case the antagonism elicited was competitive. Therefore caution is indicated in the use of pimozide to provide indirect proof of the existence of peripheral dopamine receptors.

BEHAVIOR SYNDROME IN FEMALE LIPODYSTROPHY PATIENTS RECEIVING NEUROLEPTIC DRUGS

Pimozide, an antipsychotic neuroleptic drug, administered to a young girl with generalized lipodystrophy (GLD) Induced a beneficial effect (Pediat.Res.8:435, 1974). When we administered pimozide to other lipodystrophy patients, the drug produced in affected females beyond puberty a mood change which prevented its continued use.Pimozide in low dose (1-4 mg/day) to 5 postpubescent females (3 GLD, 2 atypical lipodystrophy) produced an immediate disabling mood change characterized by catalepsy, anxiety, and sedation. These changes were not the extrapyramidal side effects produced by pimozide in high dose (>40 mg/day). In one GLD patient, the neuroleptic agents trifluropromazine and haloperidol were administered separately in low dose with effects like that of pimozide. Continued use of pimozide in the original prepubescent GLD patient has shown limited beneficial effect; now that she is entering puberty, the behavior syndrome is developing. Two males with GLD (2 and 56 years) and one prepubescent female with partial lipodystrophy, have not developed the behavior syndrome on pimozide.These observations indicate an aberrant neurohumoral etiologic mechanism in lipodystrophy and support the theory of defective hypothalmic dopamine metabolism. Absence of the behavior syndrome in a pre- and postpubescent male suggests a sex difference in hypothalamic dopamine metabolism. The findings are analogous to the induced behavior in rats injected intracerebrally with β-endorphin, a fragment of the pituitary hormone, β-lipotrophin.

The effect of dopamine on neurohypophysial hormone release in vivo and from the rat neural lobe and hypothalamus in vitro.

1. The rat hypothalamus (containing the supra-optic nuclei, paraventricular nuclei, median eminence and proximal pituitary stalk) has been incubated in vitro and shown to be capable of releasing the neurohypophysial hormones, oxytocin and arginine vasopressin, at a steady basal rate about one twentieth that of the rat neural lobe superfused in vitro. 2. The hypothalamus and neural lobe in vitro released both hormones in a similar arginine vasopressin/oxytocin ratio of about 1-2:1. However, when release was expressed relative to tissue hormone content, the hypothalamus was shown to release about three times as much arginine vasopressin and six times as much oxytocin as the neural lobe. 3. Dopamine in a concentration range of 10(-3)-10(-9)M caused graded increases in hormone release from the hypothalamus in vitro to a maximum fivefold increase over preceding basal levels. The demonstration that apomorphine also stimulated hormone release whereas noradrenaline was relatively ineffective suggested that a specific dopamine receptor was involved. A separate cholinergic component in the release process was indicated by the finding that acetylcholine stimulated release to a maximum fivefold increase in concentrations of 10(-3)-10(-9)M. 4. The fact that the isolated hypothalamus can be stimulated by dopamine and acetylcholine to release increased amount of oxytocin and arginine vasopressin raises the question of the origin and fate of the hormones released in this way. The possibility that they could be released into the hypophysial portal circulation from median eminence to affect the anterior lobe of the pituitary is discussed. 5. In similar doses, both dopamine and noradrenaline injected into the lateral cerebral ventricles of the brain of the anaesthetized, hydrated, lactating rat caused the release of arginine vasopressin and oxytocin. Apomorphine release both hormones but at a higher dose level and to less effect than the catecholamines. 6. The hormone release induced in vivo by dopamine could be prevented by the prior administration of haloperidol or phentolamine and these antagonists were equally effective in blocking the hormone release due to noradrenaline. The involvement of a specific dopamine receptor was more clearly implicated by the use of pimozide which completely inhibited the hormone release due to dopamine and apomorphine but not that due to noradrenaline. 7. It is suggested that the release of neurohypophysial hormones can be stimulated via a dopaminergic nervous pathway in addition to a cholinergic one. The possibility that the osmoreceptor mechanism for the release of antidiuretic hormone from the neural lobe of the pituitary may involve such a dopaminergic pathway is discussed.