Waiting time for surgery influences the outcome in idiopathic normal pressure hydrocephalus - a population-based study.

INTRODUCTION: Idiopathic normal pressure hydrocephalus (iNPH) is a disease that comes with a great impact on the patient's life. The only treatment for iNPH, which is a progressive disease, is shunt surgery. It is previously indicated that early intervention might be of importance for the outcome. AIM: To investigate if a longer waiting time for surgery, negatively influences the clinical outcome. METHODS: Eligible for this study were all iNPH patients (n = 3007) registered in the Swedish Hydrocephalus Quality Registry (SHQR) during 1st of January 2004-12th of June 2019. Waiting time, defined as time between the decision to accept a patient for surgery and shunt surgery, was divided into the intervals ≤ 3, 3.1-5.9 and ≥ 6 months. Clinical outcome was assessed 3 and 12 months after surgery using the modified iNPH scale, the Timed Up and Go (TUG) test and the mini mental state examination (MMSE). RESULTS: Three months after surgery, 57% of the patients with ≤ 3 months waiting time showed an improvement in modified iNPH scale (≥ 5 points) whereas 52% and 46% of patients with 3.1-5.9 and ≥ 6 months waiting time respectively improved (p = 0.0115). At 12 months of follow-up, the corresponding numbers were 61%, 52% and 51% respectively (p = 0.0536). CONCLUSIONS: This population-based study showed that in patients with iNPH, shunt surgery should be performed within 3 months of decision to surgery, to attain the best outcome.

Risk behaviours for organism transmission in daily care activities: a longitudinal observational case study.

BACKGROUND: To understand healthcare personnel's infection prevention behaviour has long been viewed as a key factor in preventing healthcare-associated infections. Suboptimal hand hygiene compliance and handling of materials, equipment, and surfaces present the main risks for potential organism transmission. Further exploration is needed regarding the role of context-specific conditions and the infection prevention behaviours of healthcare personnel. Such knowledge could enable the development of new intervention strategies for modifying behaviour. AIM: To describe risk behaviours for organism transmission in daily care activities over time. METHODS: Unstructured observations of healthcare personnel carrying out patient-related activities were performed on 12 occasions over a period of 18 months. FINDINGS: Risk behaviours for organism transmission occur frequently in daily care activities and the results show that the occurrence is somewhat stable over time. Interruptions in care activities contribute to an increased risk for organism transmission that could lead to subsequent healthcare-associated infection. CONCLUSION: Interventions aimed at reducing the risks of healthcare-associated infections need to focus on strategies that address: hand hygiene compliance; the handling of materials, equipment, work clothes and surfaces; the effects of interruptions in care activities if they are to alter healthcare personnel's infection prevention behaviour sufficiently.

Target temperature 34 vs. 36°C after out-of-hospital cardiac arrest - a retrospective observational study.

BACKGROUND: Intensive care for comatose survivors of cardiac arrest includes targeted temperature management (TTM) to attenuate cerebral reperfusion injury. A recent multi-center clinical trial did not show any difference in mortality or neurological outcome between TTM targeting 33°C or 36°C after out-of-hospital-cardiac-arrest (OHCA). In our institution, the TTM target was changed accordingly from 34 to 36°C. The aim of this retrospective study was to analyze if this change had affected patient outcome. METHODS: Intensive care registry and medical record data from 79 adult patients treated for OHCA with TTM during 2010 (n = 38; 34°C) and 2014 (n = 41; 36°C) were analyzed for mortality and neurological outcome were assessed as cerebral performance category. Student's t-test was used for continuous data and Fischer's exact test for categorical data, and multivariable logistic regression was applied to detect influence from patient factors differing between the groups. RESULTS: Witnessed arrest was more common in 2010 (95%) vs. 2014 (76%) (P = 0.03) and coronary angiography was more common in 2014 (95%) vs. 2010 (76%) (P = 0.02). The number of patients awakening later than 72 h after the arrest did not differ. After adjusting for gender, hypertension, and witnessed arrest, neither 1-year mortality (P = 0.77), nor 1-year good neurological outcome (P = 0.85) differed between the groups. CONCLUSION: Our results, showing no difference between TTM at 34°C and TTM at 36°C as to mortality or neurological outcome after OHCA, are in line with the previous TTM-trial results, supporting the use of either target temperature in our institution.

Frequency of temporomandibular joint osteoarthritis and related symptoms in a hand osteoarthritis cohort.

OBJECTIVE: The prevalence of osteoarthritis (OA) in the temporomandibular joints (TMJs) in hand OA patients is largely unknown. Our aims were to explore (1) The frequency of TMJ-related symptoms and clinical findings; (2) The TMJ OA frequency defined by cone beam computed tomography (CBCT); and (3) The relationship between TMJ-related symptoms/clinical findings and CBCT-defined TMJ OA, in a hand OA cohort. METHODS: We calculated the frequencies of TMJ-related symptoms, clinical findings and diagnosis of TMJ OA by CBCT and clinical examination in 54 patients from the Oslo hand OA cohort (88% women, mean (range) age 71 (61-83) years). Participants with and without CBCT-defined TMJ OA were compared for differences in proportions (95% confidence interval (CI)) of symptoms and clinical findings. Sensitivity and specificity of the clinical TMJ OA diagnosis were calculated using CBCT as reference. RESULTS: Self-reported symptoms and clinical findings were found in 24 (44%) and 50 (93%) individuals (93%), respectively, whereas 7 (13%) had sought healthcare. Individuals with CBCT-defined TMJ OA (n = 36, 67%) reported statistically significantly more pain at mouth opening (22%, 95% CI 4-40%), clicking (33%, 95% CI 14-52%) and crepitus (25%, 95% CI 4-46%). By clinical examination, only crepitus was more common in TMJ OA (33%, 95% CI 29-77%). Clinical diagnosis demonstrated low sensitivity (0.42) and high specificity (0.93). CONCLUSIONS: CBCT-defined TMJ OA was common in hand OA patients, suggesting that TMJ OA may be part of generalized OA. Few had sought healthcare, despite high burden of TMJ-related symptoms/findings. Clinical examination underestimated TMJ OA frequency.

Fat, sugar and water intakes among families from the IDEFICS intervention and control groups: first observations from I.Family.

BACKGROUND: The objective of this paper is to investigate differences in diets of families in intervention versus control communities 5 years after the Identification and Prevention of Dietary- and Lifestyle-Induced Health Effects in Children and Infants intervention ended. METHODS: Altogether, 4,691 families from the I.Family study with at least one participating parent and one child are included in this analysis. Diet quality indicators, defined as propensities to consume fat, sugar, water and fruit and vegetables, are calculated from a 59-item food frequency questionnaire. Multilevel linear models with random intercepts for study centre are used to determine whether mean diet indicators, calculated at the family level, differed as a function of previous exposure to the intervention. RESULTS: Families in the intervention communities reported a significantly lower sugar propensity (19.8% vs. 20.7% of total food items, p < 0.01) and a higher water propensity (47.3% vs. 46.0% of total beverages, p < 0.05) compared with families in the control communities, while fat and fruit and vegetables propensities were similar. No significant diet differences between intervention and control children were present at the Identification and Prevention of Dietary- and Lifestyle-Induced Health Effects in Children and Infants baseline. DISCUSSION: This result indicates better diet quality in intervention families, which was not present in children when their diets were assessed before the intervention, and gives some cause for optimism regarding the sustainability of some aspects of the diet intervention.

Temporomandibular joint diagnostics using CBCT.

The present review will give an update on temporomandibular joint (TMJ) imaging using CBCT. It will focus on diagnostic accuracy and the value of CBCT compared with other imaging modalities for the evaluation of TMJs in different categories of patients; osteoarthritis (OA), juvenile OA, rheumatoid arthritis and related joint diseases, juvenile idiopathic arthritis and other intra-articular conditions. Finally, sections on other aspects of CBCT research related to the TMJ, clinical decision-making and concluding remarks are added. CBCT has emerged as a cost- and dose-effective imaging modality for the diagnostic assessment of a variety of TMJ conditions. The imaging modality has been found to be superior to conventional radiographical examinations as well as MRI in assessment of the TMJ. However, it should be emphasized that the diagnostic information obtained is limited to the morphology of the osseous joint components, cortical bone integrity and subcortical bone destruction/production. For evaluation of soft-tissue abnormalities, MRI is mandatory. There is an obvious need for research on the impact of CBCT examinations on patient outcome.

Craniofacial growth disturbance is related to temporomandibular joint abnormality in patients with juvenile idiopathic arthritis, but normal facial profile was also found at the 27-year follow-up.

OBJECTIVES: To assess the long-term outcome of craniofacial morphology related to disease variables and temporomandibular joint (TMJ) involvement as demonstrated with computed tomography (CT) and magnetic resonance imaging (MRI) in adult patients with juvenile idiopathic arthritis (JIA). METHODS: Sixty of 103 patients participated in a re-examination on average 27 years after baseline. Craniofacial morphology, with emphasis on size and position of the mandible, was assessed in lateral cephalographic images and related to disease variables and TMJ involvement by CT and MRI. Definitions of craniofacial growth disturbances were based on measurements outside 2 SD from the mean of healthy adult controls. RESULTS: Sagittal craniofacial growth disturbances were found in 57% and micrognathia in 27% of the 60 patients. Of those with JIA TMJ involvement, 70% had some form of growth disturbance. Micrognathia occurred only in patients with bilateral TMJ involvement. The bilateral TMJ group had significantly different craniofacial morphology than healthy controls and patients without TMJ involvement. Growth disturbances and TMJ involvement were present in all subtypes of JIA, except for one subtype comprising one patient. Patients with growth disturbances had more severe disease than patients with normal craniofacial growth, regarding both present and previous disease activity. Unexpectedly, half of the patients without craniofacial growth disturbances also had TMJ involvement, many from before the age of 12. CONCLUSIONS: Craniofacial growth disturbances were found to be frequent in adult JIA patients, especially in those with bilateral TMJ involvement. However, growth disturbances did not always follow TMJ involvement, not even when affected early.

MFP14, a multifunctional emerging protein with immunomodulatory properties, prevents spontaneous and recurrent autoimmune diabetes in NOD mice.

AIMS/HYPOTHESIS: To test the effects of multifunctional protein 14 (MFP14), which shares structural homology with heat shock proteins (HSPs), on the development of Type I (insulin-dependent) diabetes mellitus in NOD mice. METHODS: MFP14 was given to euglycaemic female NOD mice from either the 4th to the 25th or from the 12th until the 35th week, or commencing one day before islet transplantation and until the reappearance of hyperglycaemia. Pancreata from NOD mice treated with multifunctional protein 14 for 14 consecutive weeks until 18 weeks of age were examined histologically for insulitis. Anti-CD3 and/or lipopolysaccharide (LPS)-induced blood levels of interferon (IFN)-gamma, interleukin (IL)-4, IL-10, IL-12 and tumour necrosis factor (TNF)-alpha were measured by ELISA in 10 week-old female NOD mice treated for 6 consecutive weeks with either MFP14 or PBS. Unless otherwise stated, multifunctional protein 14 was administered daily 5 times a week at a dose of 25 microg. Control mice received PBS or, in selected experiments, heat-inactivated MFP14. RESULTS: MFP 14 treated mice had a significantly lower incidence of spontaneous diabetes compared to control mice. The MFP14 was equally effective both upon early and late prophylaxis and the protection persisted until week 50 in mice treated from weeks 4 to 25. Insulitis was significantly reduced by the MFP14. The MFP14 also delayed recurrence of hyperglycaemia in syngeneic islet-transplanted NOD mice. Although MFP14 reduced anti-CD3 and/or LPS-induced blood levels of IFN-gamma, TNF-alpha and IL-12 it increased IL-4 and IL-10. CONCLUSION/INTERPRETATION: The MFP14 could be a possible candidate for the prevention or early treatment of human Type I (insulin-dependent) diabetes mellitus.

A longitudinal cohort study of elderly women with urinary tract infections.

AIMS: the prevalence of urinary tract infections (UTI), urinary incontinence (UI), estrogen-use and overall mortality in a cohort of elderly women who had been treated for UTI in 1985-86 was re-assessed 10 years later. MATERIAL AND METHODS: a random sample of 6000 women from the birth cohorts 1900, 1905, 1910, 1915 and 1920 were invited in 1986 to complete a questionnaire about UTI, UI and estrogen use (response rate 70%; n = 4206). Treatment with antibiotics for UTI during 1985-86 was reported by 688 (17%) women. In 1995 a similar questionnaire was sent to the women from this group who were still alive (n = 434). Mortality in the women with a history of UTI was compared with an aged-matched control group of women who did not have UTI during 1985-86. RESULTS: the questionnaire was completed and returned by 361 (83%) women. Treatment for at least one UTI during the last 9 years was reported by 219 (61%) women. The number of episodes varied: 35% had one to two UTI, 28% had three to four UTI, 27% five to ten UTI and 10% had had more than 10 UTI. In 1986, the prevalence of UI was higher in women with a history of UTI than in the total population sample (30 vs. 17%; P < 0.001). The prevalence of UI had increased from 30% in 1986 to 33% in 1995 (P < 0.05). Mortality in the women with a history of UTI was higher than in the aged-matched control group (37 vs. 28%; P < 0.001). A total of 162 (45%) women had received estrogen therapy at some time after the age of 60 years and 140 (39%) reported that they were currently taking low potency estrogens. CONCLUSION: elderly women with a history of UTI had a continued high occurrence of UTI and UI, and overall mortality was higher in these women than in an age-matched control group of women from the total population.

Preparation and purification of an end to end coupled mEGF-dextran conjugate.

The amino terminus of mouse epidermal growth factor (mEGF) was coupled directly to the aldehyde end of dextran through a reductive amination procedure. The highest coupling efficiency was approximately 80% and could be reached after approximately 24 h of reaction time at pH 8. Gel filtration on Sephadex G-50 Fine removed free mEGF from the conjugate. Preparative polyacrylamide gel electrophoresis was used to separate the conjugate from excess noncharged dextran. The conjugate bound specifically to the EGF receptor on cultured glioma cells as shown in displacement tests with free mEGF. The conjugate was stable in the pH interval 4-9, in 2 M sodium chloride, in 7 M urea, and in human serum and could still bind to the EGF receptor after such treatments. The conjugates are candidates for targeted nuclide therapy.

trans-2-Aryl-N,N-dipropylcyclopropylamines: synthesis and interactions with 5-HT(1A) receptors.

Twelve N,N-dipropyl-substituted derivatives of trans-2-arylcyclopropylamine have been prepared and assayed for their ability to displace [(3)H]-8-OH-DPAT from rat brain 5-HT(1A) receptors. The new derivatives include phenyl (7a), bromo- (7b) and fluorophenyl (7c-e), 2-methoxy-5-fluorophenyl (7h), and 2-hydroxy-5-fluorophenyl (7l) as well as trifluoromethylphenyl (7f) and 2,3-dichlorophenyl (7g) analogues. In the present series of compounds, electron-withdrawing substituents in the phenyl ring appear to decrease the affinity for 5-HT(1A) receptors. In contrast, electron-rich aryl groups, such as 2- or 3-thienyl (7j and 7k, respectively), provide compounds with high affinity. The additional bulk produced by the aromatic moiety in the 2-benzothienyl derivative 7i appears to be detrimental to 5-HT(1A) receptor affinity. The racemic mixtures of the interesting 7j and 7l were resolved into the enantiomers; 7j and 7l exhibited a high enantiomeric 5-HT(1A) receptor affinity ratio (75-fold and 100-fold, respectively). The enantiomers of 7j and 7l were evaluated in vivo by use of biochemical and behavioral tests in rats. Compound (1R,2R)-7j behaved as a partial agonist whereas (1R,2S)-7l appeared as an efficacious 5-HT(1A) receptor agonist, stimulating both autoreceptors and postsynaptic receptors.

Effect of microwave radiation on permeability of liposomes. Evidence against non-thermal leakage.

The effect of 2.45 GHz microwave radiation on the permeability of unilamellar phosphatidylcholine liposomes has been studied. Leakage of 5(6)-carboxyfluorescein from the liposomes was measured using spectrofluorimetry after exposure to either microwaves or thermal heating for 5-20 min intervals. The exposure temperature, 37.6 +/- 0.5 degrees C, was well above the phase transition temperature of the lipid membrane. The microwave exposure did not result in any non-thermal increase in permeability above that produced by thermal heating. This study refutes the results reported by Saalman et al. [1] in which an increased liposome permeability due to microwave exposure was reported. The refined analysis in the present study shows that this increased liposome permeability was not a non-thermal microwave effect.

The influence of age, parity, oral contraception, hysterectomy and menopause on the prevalence of urinary incontinence in women.

The influence of age, parity, duration of previous oral contraceptive use, hysterectomy and menopause on the prevalence of urinary incontinence was evaluated by means of a postal questionnaire in women 46 to 86 years old who resided in the city of Göteborg, Sweden. A sample of 10,000 women from the 7 birth cohorts of 1900 to 1940 was obtained at random from the population register. The overall response rate was 74.6%. The prevalence of urinary incontinence increased (p < 0.001) in a linear fashion from 12.1% in the 1940 birth cohort to 24.6% in the 1900 birth cohort. The prevalence of urinary incontinence in nulliparous women was 7.7% in the 1930 birth cohort and 5.5% in the 1940 birth cohort. The corresponding figures for women who had experienced 1 delivery were 11.1% and 10.6%, compared to 14.0% and 16.4% among women who had had 3 or more deliveries. Urinary incontinence was more prevalent in women who had undergone hysterectomy (p < 0.05). The prevalence of urinary incontinence was unaffected by the duration of previous oral contraceptive use and there was no evidence to suggest that the prevalence of urinary incontinence increased at the time of the last menstrual period.

Factors influencing vaginal cytology, pH and bacterial flora in elderly women.

OBJECTIVE: To evaluate factors influencing the vaginal micro-environment in elderly women. STUDY DESIGN: Vaginal pH, cytology (Karyopyknotic index, KPI) and bacterial cultures were assessed in 350 women (age 72.2 +/- 1.4 years, range 65-84 years) who were not taking estrogens. RESULTS: Vaginal pH was 6.5 +/- 0.1, KPI was 3.0 +/- 0.9% and bacteria of fecal type dominated. However, in some women the vaginal micro-environment resembled that of fertile women, with a predominance of lactobacilli (n = 68), low pH (n = 41) and an increased maturation index (n = 57). KPI was higher (p < 0.001) in women weighing > or = 85 kg, or with a body mass > or = 9th decentile or with a diastolic blood pressure > or = 100 mmHg and in women (p < 0.05) with a high menopausal age (> or = 53 years). Vaginal pH was lower (p < 0.001), KPI was higher (p < 0.01) and there was an increased (p < 0.05) presence of lactobacilli in smokers compared to non-smokers. CONCLUSIONS: The latter finding is somewhat paradoxical as cigarette smoking has previously been shown to negatively influence estrogen metabolism. The influence of cigarette smoking on the vaginal micro-environment may be a direct local effect of nicotine.

Intrinsic activity of enantiomers of 8-hydroxy-2-(di-n-propylamino)tetralin and its analogs at 5-hydroxytryptamine1A receptors that are negatively coupled to adenylate cyclase.

Although many different types of compounds have been tested for 5-hydroxytryptamine1A (5-HT1A) binding affinity, much remains to be learned about the structural requirements associated with 5-HT1A agonism, partial agonism, and antagonism. The present study uses the forskolin-stimulated adenylate cyclase (FSC) assay as a functional screen in rat hippocampal membranes to examine structure-activity relationships for a series of enantiomers of novel analogs of the prototypic 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). The findings illustrate that there can be large enantiomeric differences in intrinsic activity at the 5-HT1A receptor, independent of enantiomeric effects on binding affinity. Generally, for each enantiomeric pair exhibiting stereoselective 5-HT1A binding, the enantiomer with the higher affinity also displayed the greater amount of 5-HT1A intrinsic activity in the FSC assay. Interestingly, the enantiomers of 8-OH-DPAT itself displayed stereoselective differences in intrinsic activity but not 5-HT1A affinity. Several of the compounds, namely (S)-UH-301, (2R,3R)-CM-12, and (1S,2R)-LEA-146, may have potential as prototypes for selective 5-HT1A antagonists, and (S)-UH-301 itself may be useful as a selective 5-HT1A antagonist. The FSC data presented here are in good agreement with reported measures of in vivo 5-HT1A activity, which were in part the basis of a recently proposed model for the 5-HT1A pharmacophore [J. Med. Chem. 34: 497-510 (1991)].

Effect of 2.45 GHz microwave radiation on permeability of unilamellar liposomes to 5(6)-carboxyfluorescein. Evidence of non-thermal leakage.

The influence of 2.45 GHz microwave radiation on the membrane permeability of unilamellar liposomes was studied using the marker 5(6)-carboxyfluorescein trapped in phosphatidylcholine liposomes. The release of the fluorescent marker was followed by spectrofluorimetry after an exposure of 10 minutes to either microwave radiation or to heat alone of the liposome solutions. A significant increase of the permeability of carboxyfluorescein through the membrane was observed for the microwave-exposed samples compared to those exposed to normal heating only. Exposure to 2.45 GHz microwave radiation of liposomes has been previously found to produce increased membrane permeability as compared with heating. However, in contrast to previous studies, the observations reported here were made above the phase transition temperature of the lipid membrane. The experimental setup included monitoring of the temperature during microwave exposure simultaneously at several points in the solution volume using a fiberoptic thermometer. Possible mechanisms to explain the observations are discussed.

A 3-D model for 5-HT1A-receptor agonists based on stereoselective methyl-substituted and conformationally restricted analogues of 8-hydroxy-2-(dipropylamino)tetralin.

The enantiomers of cis- and trans-1,2,3,4,4a,5,10,10a-octahydro-9-hydroxy-1- propylbenzo[g]quinolines (10 and 11, respectively) and the enantiomers of trans-1,2,3,4,4a,5,6,10b-octahydro-10- hydroxy-4-propylbenzo[f]quinoline (12) have been synthesized and their stereochemical and conformational characteristics have been studied by use of X-ray crystallography and molecular mechanics (MMP2) calculations. The compounds, which are conformationally restricted analogues of the potent 5-hydroxytryptamine (5-HT) receptor agonist 8-hydroxy-2- (dipropylamino)tetralin (8-OH-DPAT; 1) have been evaluated for central 5-HT and dopamine receptor stimulating activity by use of biochemical and behavioral tests in rats. In addition, we have evaluated the ability of these compounds and a number of previously reported analogues to displace [3H]-8-OH-DPAT from 5-HT1A-binding sites. The enantiomers of 12 behave as potent 5-HT1A-receptor agonists, whereas the octahydrobenzo[g]quinoline derivatives are much less potent or inactive. In general, the affinities of the compounds correlate well with their agonist potencies. The set of compounds under study is accommodated by a novel computer-graphics-derived model for 5-HT1A-receptor agonism. The model consists of a flexible pharmacophore and a partial receptor-excluded volume.

A health care program for the investigation and treatment of elderly women with urinary incontinence and related urogenital symptoms.

The assessment and treatment of urinary incontinence and related urogenital symptoms using an algorithm model was evaluated in 364 elderly women complaining of urinary incontinence. The women (age 72.1 +/- 1.5 years, range 65-84 years) were assessed by a 48-hour pad test, a cough provocation test, micturition lists and a gynecological examination which included a smear test, measurement of vaginal pH and bacterial cultures. The diagnosis of urinary incontinence was confirmed in 346 women (stress 26.3%; urge: 32.7%; mixed: 41.0%). Women suffering from stress incontinence were younger (p less than 0.05) and had experienced a larger number of deliveries (p less than 0.05) than women with urge incontinence. All the women were treated with oral estriol, 3 mg daily for 4 weeks followed by 1-2 mg daily. The total urinary leakage per 48 hours (p less than 0.01) and maximum single leakage (p less than 0.05) were reduced in women with mixed incontinence, while the frequency of micturition decreased (p less than 0.05) in women with urge incontinence after 12 weeks treatment with oral estriol. There were no significant changes in any of the objective micturition parameters in women with stress incontinence following treatment. Karyopyknotic index and the presence of lactobacilli were increased (p less than 0.001), and vaginal pH decreased (p less than 0.001) following treatment in women with all types of incontinence. More than 70% of all the women treated in this algorithm model judged themselves to be improved, much improved or cured.

Effects of stereoselective 5-HT1A agonists on male rat sexual behavior.

The effects on male rat sexual behavior of some new stereoselective 5-HT agonists, related to 8-OH-DPAT, are presented. It was found that (+)cis-8-hydroxy-1-methyl-2-(di-n-propylamino) tetralin (8-OH-MeDPAT), as well as (-)trans-2-(2-hydroxyphenyl)-N,N-di-n-propylcyclopropylamine (2-OH-DCPA), and its 3-hydroxy-phenyl analog (3-OH-DCPA), stereoselectively facilitated the male rat sexual behavior, as evidenced by a decrease in the number of intromissions preceding ejaculation, and a shortening of the ejaculation latency. For the former two compounds, studied in further detail, the potency and efficacy appear to be of the same magnitude as previously found for 8-OH-DPAT. The results demonstrate specific 5-HT receptor involvement in the mediation of male rat sexual behavior.

N,N-Dialkylated monophenolic trans-2-phenylcyclopropylamines: novel central 5-hydroxytryptamine receptor agonists.

N,N-Dialkylated monophenolic derivatives of trans-2-phenylcyclopropylamine were synthesized and tested for central 5-hydroxytryptamine (5-HT) and dopamine (DA) receptor stimulating activity by use of a biochemical test method in rats. A hydroxy substituent in the 2- or 3-position of the phenyl ring was required for 5-HT-receptor stimulation. N,N-Diethyl or N,N-di-n-propyl substitution gave the most potent 5-HT-receptor agonists. The 4-hydroxy and 3,4-dihydroxy derivatives of trans-2-phenyl-N,N-di-n-propylcyclopropylamine were inactive at central DA and 5-HT receptors. In contrast, the corresponding 3-hydroxy derivative 18 and some of its derivatives weakly affected both DA and NE synthesis. Two of the most potent 5-HT-receptor agonists, trans-2-(2-hydroxyphenyl)-N,N-di-n-propylcyclopropylamine (8) and the 3-hydroxy isomer 18 were resolved into the enantiomers. The 1R,2S enantiomers of 8 and 18 displayed 5-HT activity, while the 1S,2R enantiomers were inactive. Compound (1R,2S)-18, but not (1R,2S)-8, weakly affected rat brain DA and NE synthesis.