Sublingual apomorphine as a neuroendocrine probe Ludmila Brunerova a, b, ⁎, Jana Potockova b , Jiri Horacek c , Helena Koprivova d , Milan Rehula e , Michal Andel b a Mediscan, Euromedic, Prague, Czech Republic b Centre for the Research of Diabetes, Metabolism and Nutrition, II. Department of Medicine, Faculty Hospital Kralovske Vinohrady and 3rd Faculty of Medicine, Charles University, Prague, Czech Republic c Psychiatric Centre Prague, 3rd Faculty of Medicine, Charles University, Prague, Czech Republic d Department of Chemistry and Biochemistry, Faculty Hospital Kralovske Vinohrady and 3rd Faculty of Medicine, Charles University, Prague, Czech Republic e Faculty of Pharmacy, Charles University, Hradec Kralove, Czech Republic abstract article info Article history: Received 21 March 2010 Received in revised form 14 September 2011 Accepted 22 September 2011 Keywords: Sublingual apomorphine Neuroendocrine probe Prolactin Growth hormone Subcutaneous apomorphine, a dopaminergic agonist, is used as a neuroendocrine probe for assessing central dopaminergic activity. The aim of our study was to test sublingual apomorphine for the same purpose. We administered sublingual apomorphine in a weight-dependent dose (0.033 mg/kg) to 42 healthy men. Prolac- tin and growth hormone levels were measured before and after the administration at 15, 30, 45, 60, 75, 90, 120, 150 and 180 min. Subjects filled in Zung's self-assessment scores of anxiety (SAS) and depression (SDS) questionnaires before and after the test. Areas under the curve for prolactin and growth hormone levels were calculated using the trapezoidal rule. All subjects showed decreased prolactin, and 40/42 subjects showed increased growth hormone, in response to sublingual apomorphine. Average peak value for prolactin was -4.6 ± 1.8 μg/l. Average peak value for growth hormone was 8.1 ± 8.5 ng/ml for the whole group, and 9.6 ± 8.1 ng/ml after exclusion of two negative growth hormone responders. Sublingual apomorphine pro- duced no major side effects. Significant decreases in SAS (21.5 ± 5.7 vs. 20.6 ± 5.5) and SDS (9.7 ± 7.8 vs. 7.8 ± 6.8) scores were observed after the test. Sublingually administered apomorphine appears to be well tol- erated and useful as a neuroendocrine marker of central dopaminergic activity. © 2012 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Acute administration of drugs that increase central dopamine (DA) function can influence the secretion of certain anterior pituitary hormones, notably prolactin (PRL) and growth hormone (GH). These drugs are used as pharmacological probes in DA challenge tests (Duval et al., 2000; Pitchot et al., 2001a,b, 2003; Duval et al., 2006). Changes in hormones thus can be used as markers of central dopami- nergic activity. For assessing central dopaminergic functions, the DA agonist apomorphine has been used. Apomorphine is mostly a dopa- minergic (D) 2 receptor agonist, and its acute administration leads to increased GH levels and decreased PRL levels. Until recently, only subcutaneous apomorphine has been used, and its administration can produce certain negative side effects. It has been difficult (at least in the Czech Republic) to gain access to the par- enteral form of apomorphine. On the other hand, sublingual apomor- phine was widely available, as it was used as a drug for treatment of erectile dysfunction in 2-, 3- and 4-mg doses (Uprima®, Abbott), and was very well tolerated. The aim of our study was to test the possibility of using sublingual apomorphine as a neuroendocrine probe of dopaminergic activity. 2. Methods 2.1. Subjects The study was performed on 42 healthy, male, non-smoker volunteers recruited from middle Bohemia through advertisements. The average age of the participants was 43.5 ± 7.4 years, and the average body mass index (BMI) was 27.4 ± 5.7 kg/m². The study was approved by the local Ethics Committee and respected the principles of the Helsinki Declaration. All subjects underwent prior physical examination by a physician, and blood tests for routine metabolic measures were performed. 2.2. Sublingual apomorphine Since there were large differences in body weight among the subjects, and because GH and PRL responses to dopaminergic stimulation are different in obese and very thin people (Pearson correlation: r =-0.53, P = 0.0001, our own unpublished data), we used individualized doses for each subject based on body weight. Sublingual adminis- tration of apomorphine has a bioavailability of 17–18% compared with subcutaneous administration (www.pom.go.id/io/monograf/Uprima.html, n.a). Thus, we calculated a 2.77-mg dose of sublingual apomorphine to be equivalent to 0.5 mg of subcutaneous apomorphine, which was the lowest dose used in previous studies as a neuroendocrine probe. A dose of 2.77 mg was the lowest used in our study (for the thinnest subject), which represented 0.033 mg/kg of sublingual apomorphine. According to this formula, individualized weight-adjusted sublingual tablets of apomorphine hydrochloride hemihydrate were prepared from original sublingual tablets (Uprima®) for each Psychiatry Research 198 (2012) 297–299 ⁎ Corresponding author at: II. Department of Medicine, 3rd Faculty of Medicine, Charles University and University, Hospital Kralovske Vinohrady, Srobarova 50, 100 34 Prague, Czech Republic. Tel.: +420 723958280,++420 267162710 Tel./fax: +420 267162710. E-mail address: brunerova@seznam.cz (L. Brunerova). 0165-1781/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.psychres.2011.09.022 Contents lists available at SciVerse ScienceDirect Psychiatry Research journal homepage: www.elsevier.com/locate/psychres