[Does fenclonine open up new perspectives in the treatment of impotence?].
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Adult↗
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Results for “Fenclonine”
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Clinical and biochemical effects of fenclonine: a serotonin depletor.
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Adult↗
Prostaglandins: antinociceptive effect of prostaglandin E1 in the rat.
1. The antinociceptive effect of prostaglandins E1, E2 and F2alpha was studied in albino rats. Though all three prostaglandins produced similar degrees of sedation, only prostaglandin E1 (PGE1) produced a dose-related antinociceptive activity. 2. The antinociceptive activities of equi-analgesic doses of morphine (7.5. mg/kg, i.p.) and PGE1 (2.0 mg/kg, i.p.) were inhibited to almost similar extents after pretreatment with drugs known to reduce central turnover of serotonin receptors, namely reserpine, fenclonine (p-chlorophenylalanine), methysergide and 5,6-dihydroxytryptamine. 3. Prostaglandin F2alpha (2.0 mg/kg, i.p.) significantly inhibited the antinociceptive effects of both morphine and PGE1. 4. The prostaglandin synthesis inhibitors, indomethacin and diclofenac, significantly inhibited morphine analgesia. 5. Probenecid markedly prolonged the duration of antinociceptive effect of morphine and the duration of PGE1-induced potentiation of subanalgesic dose of morphine. 6. The results suggest that, in albino rats, PGE1-induced antinociceptive activity is serotonin mediated and that morphine analgesia is not only mediated through serotonin but also through prostaglandins (PGE1 ?) and 5-hydroxyindole acetic acid, the serotonin metabolite.
Analgesics↗
Role of hepatic arterial embolisation in the carcinoid syndrome.
Eighteen patients with severe symptoms of the carcinoid syndrome were assessed for hepatic embolisation. Four were too ill, and one had mild symptoms; thus 13 received a periembolisation regimen of cyproheptadine, fenclonine, aprotinin, methylprednisolone, tobramycin, flucloxacillin, and metronidazole. Embolisation was not performed in one patient with an occluded portal vein and was unsatisfactory in two others, in one because she was moribund and in the other because the hepatic artery had been ligated. Dramatic improvement in symptoms occurred in the nine patients in whom embolisation was successfully carried out, with abolition of flushing, severe abdominal pain, and wheeze and reduction in diarrhoea from 10.5 (SD 7.6) to 1.6 (0.9) stools/day. Urinary excretion of 5-hydroxyindole acetic acid fell from 1048 (716) to 289 (184) mumol/24 h (200 (137) to 55 (35) mg/24 h). Complications included one death from septicaemia, a hepatic abscess requiring surgical drainage, abdominal pain in three patients, pleural effusion in two, and transient encephalopathy in one. Relief of symptoms lasted for one to 24 months, and second embolisation in two patients produced further remissions of four to six months. Five patients died, one to 40 months after embolisation, in four cases because of metastases or heart failure. Hepatic embolisation is the treatment of choice for symptoms of the carcinoid syndrome resistant to medical treatment.
Adult↗
Effect of 5-HT on pain modulation of substance P in spinal cord of rats.
AIM: To study the effect of serotonin (5-HT) on pain modulation of substance P (SP) in spinal cord of rats. METHODS: Using immunohisto-chemistry and measurement of pain threshold. RESULTS: The c-fos expression evoked by intrathecal injection (it) SP 10 micrograms and sc 5% formaldehyde (For) 150 microL in the hindpaw was densely distributed in the laminae I, II, V, and VI of spinal dorsal horn. The pain threshold in the SP group was decreased while the pain intensity rating measured by behavioral method in the For group was increased. The c-fos expression induced by it 5-HT 20 micrograms was mostly distributed in the spinal dorsal horn in laminae III-IV and the pain threshold was increased. SP and For induced c-fos expressions in the spinal cord and the pain responses were reduced by 5-HT and increased by 5-HT depletor fenclonine 300 mg.kg-1. CONCLUSION: SP mainly played an algogenesia in the spinal cord. 5-HT inhibited the c-fos expression in the spinal cord evoked by SP and participated in pain modulation of SP.
Animals↗
Anxiogenic effect of naltrexone in social interaction test in rats.
AIM: To study the anxiogenic effect of naltrexone (Nal) on the emotional state of rats. METHODS: The duration of active interaction was measured in the social interaction test in rats. RESULTS: Without influence on the locomotor activity, Nal (0.1-50 mg.kg-1) dose- and time-dependently decreased the duration of active interaction, which was antagonized by morphine (5 mg.kg-1) or fenclonine (Fen, 150 mg.kg-1 x 3 d) and was enhanced by 5-hydroxytryptophan (5-HTP, 50 mg.kg-1). CONCLUSION: Nal produced anxiety via its blockade of opioid receptors; central opioidergic neurons were involved in the regulation of anxiety through their tonic inhibitions in serotonergic neurons.
Animal Communication↗
Serotonergic mechanisms in Parkinson's disease.
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Aged↗
Screening of antiserotoninergic drugs with the genetically dystrophic chicken.
Line 413 early-onset, genetically homozygous dystrophic chickens were given twice-daily intraperitoneal injections of the antiserotoninergic drugs p-chlorophenylalanine hydrochloride, fluoxetine hydrochloride, ergonovine maleate, nortriptyline hydrochloride, methiothepin maleate, and methysergide bimaleate in combination with penicillamine. Except in one case, treatment with drugs significantly prolonged the righting ability of the treated dystrophic chickens, as measured by a periodic standardized flip-test procedure. Abnormally high levels of plasma creatine phosphokinase, lactate dehydrogenase, and SGOT were found in the untreated dystrophic chickens. However, of the drug-treated dystrophic chickens, in some cases the plasma enzyme activities were reduced whereas in others they were enhanced. In agreement with previous findings, the blood serotonin levels of the dystrophic chickens were found at all age groups to be significantly higher than those in the corresponding normal chickens. This phenomenon may in part account for the improvement in righting ability demonstrated in the dystrophic chickens receiving treatment with antiserotoninergic drugs.
Animals↗
Brain biogenic amine depletion and mood.
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Affective Symptoms↗
Parachlorophenylalanine reversal of tranylcypromine effects in depressed patients.
Hospitalized bipolar and unipolar endogenously depressed patients who showed an antidepressant response to the monoamine oxidase (MAO) inhibitor, tranylcypromine sulfate, relapsed (ie, depression returned) when relatively small doses of parachlorophenylalanine (PCPA) were added for brief periods. Considered together with our findings that PCPA similarly reversed the antidepressant effects of the tricyclic drug, imipramine hydrochloride, implications are (1) serotonergic mechanisms are likely involved in the antidepressant effects of both the tricyclic drugs and MAO inhibitors in man and (2) this indolamine may also play a role in the endogenous clinical state of depression.
Bipolar Disorder↗
Serotonin depletion in the adult rat produces differential changes in highly polysialylated form of neural cell adhesion molecule and tenascin-C immunoreactivity.
Levels of immunoreactivity for highly polysialylated neural cell adhesion molecule (PSA-NCAM), NCAM, and tenascin-C (TN-C), were examined in the basal ganglia regions and hypothalamic nuclei of adult rats after serotonergic (5-HT) lesions induced by 5,7-dihydroxytryptamine injections in the dorsal and medial raphe nuclei. Decreases in the density of serotonin fibers were associated with no changes in NCAM and general decreases in PSA-NCAM staining, the time-course of changes being selective for each region. Taken that the confocal analysis indicated that serotonin neurons do not express PSA-NCAM and that similar decreases in PSA-NCAM staining were observed after inhibition of 5-HT synthesis induced by parachlorophenylalanine administration, these results suggest that 5-HT may reduce adhesion by acting on PSA-NCAM expression in its environment, and thus facilitate plasticity in adult brain. Two months after the neurotoxin lesions, a normalization of PSA-NCAM staining was associated with a partial restoration in 5-HT fiber density in the nucleus accumbens and the supraoptic nucleus, suggesting that PSA-NCAM may facilitate sprouting of 5-HT fibers. Since a similar normalization was also detected in the suprachiasmatic nucleus, which remained deprived of serotonin fibers, negative factors are likely to be involved in regeneration processes. Indeed, increases in glial fibrillary acidic protein (GFAP) followed by increases in TN-C were observed in these areas, suggesting that the secretion of TN-C by astrocytes may have negative consequences on the sprouting of 5-HT fibers. Finally, the lack of changes in striatal PSA-NCAM or TN-C staining observed after selective lesions of the dopaminergic pathway induced by intranigral injections of 6-hydroxydopamine indicates that 5-HT has a selective and critical role in adult brain plasticity.
5,7-Dihydroxytryptamine↗
The depletion of brain serotonin levels by para-chlorophenylalanine administration significantly alters the activity of midbrain dopamine cells in rats: an extracellular single cell recording study.
In this study, we examined the effect of 5-HT depletion produced by the acute administration of para-chlorophenylalanine (PCPA) on the number of spontaneously active dopamine (DA) cells in the ventral tegmental area (VTA or A10) and substantia nigra pars compacta (SNC or A9) in the rat. We also determined the effect of PCPA administration on the spike discharge pattern of midbrain DA cells. This was accomplished using standard extracellular single cell recording techniques. The administration of PCPA (400 mg/kg, i.p., 24 h before the experiment) produced a significant decrease in the number of spontaneously active DA cells in both the A9 (52%) and A10 (63%) areas compared to controls. The burst firing analysis indicated that there was a significant increase in the mean interspike interval of A9 and A10 DA neurons in PCPA treated animals compared to controls. Furthermore, a decrease in the percentage of A10 DA neurons exhibiting a burst firing pattern and the number of bursts was observed in the PCPA treated animals compared to controls. The intravenous (i.v.) administration of 5-hydroxytryptophan (40 mg/kg) and the peripheral aromatic acid decarboxylase inhibitor benserazide (10 mg/kg) which restores 5-HT content, reversed the decrease in the number of spontaneously active A9 and A10 DA neurons, as well as the decrease in the percentage of A10 DA neurons exhibiting a bursting pattern. In contrast, the i.v. administration of benserazide (10 mg/kg) and L-DOPA (40 mg/kg) did not reverse the decrease in the number of spontaneously active midbrain DA neurons produced by PCPA treatment. The pretreatment of animals with PCPA did not alter the sensitivity of spontaneously active A9 or A10 DA cells to the intravenous administration of (+)-apomorphine (1-32 micrograms/kg) compared to controls. Overall, our results indicate that the depletion of brain 5-HT by PCPA produces a decrease in the activity of midbrain DA cells, suggesting that endogenous 5-HT is required to maintain DA tone.
5-Hydroxytryptophan↗
Indirect evidence for an association of 5-HT(1B) binding sites with retinal and geniculate axon terminals in the rat suprachiasmatic nucleus.
The purpose of the present study was to investigate the possible cellular location of 5-HT(1B) receptors on retinal and geniculate afferents in the rat suprachiasmatic nucleus (SCN). Biocular enucleation significantly decreased 5-HT(1B) binding site labeling (35%), specifically in the ventral part of the SCN, while monocular enucleation produced a decrease of smaller magnitude (12%), limited to the ventral part of the contralateral SCN, these results being consistent with the known distribution of retinal afferents in the nucleus. By contrast, bilateral geniculate lesion did not induce any significant variation of 5-HT(1B) binding site labeling in the SCN. Previously, we reported that serotonin (5-HT) synthesis inhibition by parachlorophenylalanine increases 5-HT(1B) binding site labeling in the SCN. Using saturation studies, we have now demonstrated that this upregulation reflected an increase in the total number of 5-HT(1B) binding sites (+41% in the dorsal and +67% in the ventral part of the SCN). Furthermore, we evaluated the effects of bilateral geniculate lesion after 5-HT stores depletion in order to overcome problems of technical resolution limits. The magnitude of upregulation was significantly decreased (27%) after bilateral geniculate lesion, suggesting that part of the 5-HT(1B) receptor population was located on geniculate axon terminals within the SCN. The possible involvement of 5-HT(1B) receptors, according to their cellular locations evidenced in the present study, in photic and nonphotic entrainment of the circadian clock is discussed.
Afferent Pathways↗
Dopamine and serotonin in the larval CNS of a drosophilid fly, Chymomyza costata: are they involved in the regulation of diapause?
Developmental profiles of dopamine (DA) and serotonin (5-hydroxytryptamine, 5-HT) in the larval CNS of Chymomyza costata were measured by HPLC using electrochemical detection. Larvae of two strains, wild-type (W) and nondiapause mutant (M), were maintained either under long-day (LD, inducing pupariation) or short-day (SD, inducing diapause in W-strain) photoperiods. The levels of DA ranged from 10 fmol/CNS (early 3rd instar larvae) to 60 fmol/CNS (150-day-old diapausing larvae); the range for 5-HT was from 10 fmol/CNS to 75 fmol/CNS in the same larvae. During the 3rd larval instar, which is the decisive stage for photoperiodic induction of diapause, no differences were found in DA developmental profiles between different strains or conditions. Some differences were found in 5-HT developmental profiles, but only after the end of sensitive stage, and were therefore regarded as insignificant for regulation of developmental mode. Similarly, no clear correlations between the developmental profiles of DA and 5-HT and the course of developmental changes during the maintenance and termination of a few-month-long larval diapause were observed. Furthermore, the DA and 5-HT levels in the CNS were pharmacologically manipulated by feeding the larvae with either precursors or enzyme inhibitors of DA and 5-HT biosynthesis. Although retardations of growth and development were observed, the treated larvae retained full capacity for the photoperiodic response, irrespective of the level of DA or 5-HT in their CNS. Larvae with their 5-HT depleted to trace levels survived and were capable of diapause induction, maintenance, and termination. Depletion of DA to trace levels resulted in 100% mortality. Collectively, the present study indicates that 5-HT in the CNS is dispensable for the photoperiodic response in C. costata. More information is needed to elucidate the potential role of DA.
5-Hydroxytryptophan↗
Plasma amino acids in patients with the carcinoid syndrome.
Plasma tryptophan (Trp) is reported to be decreased in some patients with the carcinoid syndrome. To determine if the plasma levels of other amino acids are also altered in the carcinoid syndrome, we used a fas-liquid chromatographic method to determine the plasma amino acid concentration of nine patients with the carcinoid syndrome and nine age-matched healthy control subjects. In comparison to the control subjects, the patients with the carcinoid syndrome had decreased plasma concentration of valine (Val), isoleucine (Ile), lysine (Lys), and ornithine (Orn), and an increased plasma concentration of methionine (Met). With the exception of a decrease in urinary excretion of proline (Pro) and hydroxyporline (Hyp), the patients with the carcinoid syndrome had normal quantities of amino acids in their urine. Plasma Met returned to normal when serotonin production by the tumor was reduced 60% by parachlorophenylalanine (PCPA); the other amino acid abnormalities persisted. Further studies are needed to determine the significance of these amino acid abnormalities.
Aged↗
Monoamines and sexual behaviour in non-human primates.
The experiments described were concerned with elucidating the involvement of monoamines in the sexual behaviour of rhesus monkeys. The measurement of perturbations in the levels and turnover of the acid metabolites of serotonin and dopamine in cisternal cerebrospinal fluid, occurring in response to hormonal manipulations which alter proceptivity and receptivity, has not clarified the ways in which hormones and amines interact. However, the use of psychoactive drugs which alter the activity of monamine neurons in the brain has demonstrated that sexual activity can be profoundly influenced by such procedures. Thus, depletion of serotonin (5-hydroxytryptamine) in the brain using p-chlorophenylalanine reversed the decrease in proceptivity that followed adrenalectomy. Conversely, inhibition of serotonin uptake using chlorimipramine reduced proceptivity and receptivity to very low levels. Both findings point to the apparently important role of serotoninergic neurons in the control of sexual behaviour. Low doses of the dopamine agonist alpha-bromocriptine enhanced the proceptivity of female rhesus monkeys but high doses had no such effect. This behavioural change was not related to the concomitant suppression of serum prolactin and may have been related to presynaptic actions of the drug in a manner postulated to explain similar behavioural effects in rats. The beta-blocker oxprenolol had the interesting property of improving the sexual performance of male rhesus monkeys, a behavioural effect consistent with an anxiolytic action, although endocrine (prolactin, cortisol) measures did not provide support for such a view. Defining the nature of the interaction between hormones and monoamine-containing neurons in the brain in behavioural contexts is shown to depend largely on the application of precise neuroanatomical and neuropharmacological techniques. However, the use of systemic treatment with psychoactive drugs used widely in clinical practice, in carefully controlled, behavioural and and endocrine experiments, is likely to provide invaluable information on where and how to investigate the neural mechanisms involved.
Adrenalectomy↗
Serotonin and seasonal variation in the pancreatic structure of bats: possible presence of serotonergic axons in the gland.
The serotonin concentration in the bat pancreas was determined at nine times during the year. Pancreatic ultrastructure was also examined. The pancreatic level of serotonin was uniform throughout the year except in late May, when it fell dramatically from a normal level of 3.14 +/- .19 mugm/gm to 0.40 +/- .05 mugm/gm. No seasonal changes in islet fine structure were found; however, the ultrastructure of exocrine cells was seen to be changed radically only in bats captured in late May. At this time, bats develop unusual cytoplasmic structures in the exocrine cells. These structures consist of membrane-limited bodies containing long, straight, and parallel paracrystalline arrays of stacked membranes and round or pleomorphic osmiophilic granules. Depletion of serotonin with reserpine or parachlorophenylalanine, or incubation of pancreatic tissue with different concentrations of serotonin, failed to provoke the formation of these structures in exocrine cells of active bats. Administration of 3H-5-hydroxytryptophan to bats, or incubation of bat pancreas with 3H-serotonin, failed to demonstrate a labeling of pancreatic exocrine cells. Incubation of the gland with 3H-serotonin, however, led to intense labeling of a subset of pancreatic terminal axons. It is concluded that the natural fall in the concentration of serotonin in late May is not the cause of the formation of the paracrystalline structures in pancreatic exocrine cells. The specific pancreatic uptake mechanism for serotonin found by Kovary et al. ('80) is probably a property of pancreatic neurites; these neurites might be serotonergic.
Animals↗
Amitriptyline potentiates morphine analgesia by a direct action on the central nervous system.
Trycyclic antidepressants are often effective in the management of neuropathic pains. To elucidate the mechanism of tricyclic-induced analgesia, amitriptyline and other drugs were injected into lightly anesthetized rats either systemically or via lumbar intrathecal cannulas. Analgesia was assessed by measuring the latency of the tail flick reflex. Using this model, intrathecal amitriptyline (30 micrograms) significantly enhanced the analgesic effect of an intraperitoneal dose of morphine (0.5 mg/kg) that by itself produced no measurable effect. Given systemically, amitriptyline (30 or 100 micrograms intraperitoneally) was ineffective. Cocaine (30 micrograms) also potentiated morphine analgesia, but iprindole, a tricyclic antidepressant with a very weak inhibitory effect on monoamine uptake, was ineffective. This enhancement of analgesia by intrathecal amitriptyline was prevented by pretreating the rats with p-chlorophenylalanine (300 mg/kg). These results are consistent with the hypothesis that amitriptyline produces analgesia by blocking serotonin uptake and therefore enhancing the action of serotonin at the spinal terminals of an opioid-mediated intrinsic analgesia system.
Amitriptyline↗