Imipramine induced elevation of prolactin levels in patients with HIV/AIDS improved their immune status / La elevación de niveles de prolactina mediante inducción con imipramina mejoró el estatus inmune de pacientes con VIH/SIDA

Prolactin is known to have significant immunomodulatory properties. Imipramine, a monoamine oxidase inhibitor, stimulates prolactin production because it decreases dopamine which inhibits secretion of prolactin. The study objective was to determine if use of imipramine can result in immunological benefits for HIV-positive patients by restoration and preservation of immunological function. A cohort of 19 retroviral positive patients was identified for the prospective study which continued for a 28-week period. Three patients dropped out before the study began. Inclusion criteria accepted only patients on the same highly active antiretroviral therapy (HAART) regimen for a nine-month period and who had reached a plateau with respect to the CD4 cell count and also had no prior history of antidepressant use for a 12-month period. This study had a "before and after" design, patients serving as their own control. The study drug imipramine was prescribed for a 12-week period up to visit 4, and then discontinued for 4-weeks (washout period) at which time blood investigations were done at visit 5. Finally, patients were prescribed the study drug for a further 12-week period to the end of the trial (visit 7). At the 95 per cent probability level, significant differences in average prolactin and CD4 levels from visit 4 to the end of the trial period were recorded. Results showed a trend of prolactin levels decreasing after washout (p = 0.015) and increasing by the end of the trial period once imipramine dispensation had recommenced (p = 0.006). With respect to the CD4 cell count, there was a significant increase after wash-out (p = 0.022). These results indicate a trend to immune boosting in HIV-positive patients who had obtained the maximum response from HAART.

Se sabe que la prolactina posee importantes propiedades inmunomudolatorias. La imipramina, un inhibidor de la monoamino oxidasa, estimula la producción de la prolactina porque disminuye la dopamina, que a su vez inhibe la secreción de prolactina. El objetivo de este estudio fue determinar si el uso de la imipramina puede traer beneficios inmunológicos a los pacientes VIH positivos mediante la restauración y preservación de la función inmunológica. Se identificó una cohorte de 19 pacientes retrovirales positivos, a fin de realizar este estudio prospectivo que continuó por un período de 28 semanas Tres pacientes se retiraron antes de que el estudio comenzara. Los criterios de inclusión aceptaban sólo pacientes que tuvieran el mismo régimen de terapia antiretroviral altamente activa (HAART) por un período de nueve meses, que hubieran alcanzado un nivel de estabilización con respecto al conteo de células CD4, y que no hubieran además tenido con anterioridad una historia de uso de anti-depresantes por espacio de 12 meses. Este estudio tuvo un diseño "antes y después", sirviendo los pacientes como su propio control. La imipramina para el estudio fue prescrita por un período de 12 semanas hasta la visita 4, y luego descontinuada por 4 semanas para un reposo farmacológico (período de lavado), realizándose entonces pruebas de sangre en la visita 5. Finalmente se prescribió el medicamento de estudio a los pacientes por un nuevo período de 12 semanas hasta el final del ensayo (visita 7). En el nivel de probabilidad del 95 por ciento, se registraron diferencias significativas en los niveles promedio de prolactina y CD4 desde la visita 4 hasta el final del período de ensayo. Los resultados mostraron una tendencia de los niveles de prolactina a descender tras el lavado (p = 0.015) y a aumentar hacia el final del período de ensayo, una vez que la dispensación de imipramina hubiese recomenzado (p = 0.006). Con respecto al conteo de células de CD4, hubo un aumento significativo luego del lavado (p = 0.022).

Possible role of citalopram and desipramine against sleep deprivation-induced anxiety like-behavior alterations and oxidative damage in mice.

Sleep is an essential physiological process for maintaining physical, mental, and emotional health. Sleep deprivation and associated disorders like depression and anxiety are one of the major problems now-days. The present study was designed to explore the neuroprotecitve effect of citalopram and desipramine on 72 hr sleep deprivation-induced behavioral alterations and oxidative damage in mice. Various behavioral tests (plus maze, zero maze, mirror chamber, actophotometer), body weight followed by oxidative parameters (malondialdehyde level, glutathione, catalase, nitrite and protein) were assessed. Treatment with citalopram (5 and 10 mg/kg, ip) and desipramine (10 and 20 mg/kg, ip) for 5 days significantly improved locomotor activity, anti-anxiety like behavior in all paradigms tasks (mirror chamber, plus maze, zero maze) as compared to control (72 hr sleep-deprived). Biochemically, citalopram and desipramine treatment significantly restored depleted reduced glutathione, catalase activity, attenuated raised lipid peroxidation and nitrite level as compared to control (72 hr sleep-deprived) animals. Results of present study suggest that citalopram (5 and 10mg/kg, ip) and desipramine (10 and 20 mg/kg, ip) have neuroprotective effect against sleep deprivation-induced behavior alteration and oxidative damage in mice.

Effect of chlorpromazine, imipramine and lithium on MAO-A and MAO-B activity in rat brain mitochondria.

Drugs with efficacy in psychiatric disorders affect the function of central neurotransmitter amines, which are inactivated primarily by monoamine oxidase (MAO). Effect of these drugs on the two types of MAO (MAO-A and MAO-B) has been studied in rat brain. The result showed that chlorpromazine (CPZ) and imipramine (IMI) at concentrations of 1x10(-2), 5x10(-3) and 2.5x10(-3) M inhibited rat brain mitochondrial MAO-A activity in vitro by 82, 50, 39 and 86, 74, 38 %, respectively. CPZ at concentrations of 5x10(-3), 2.5x10(-3), 1x10(-3) M inhibited rat brain mitochondrial MAO-B activity in vitro by 83, 55, 39 %, respectively, while IMI at concentrations of 5x10(-4), 2.5x10(-4), 1x10(-4) M inhibited the in vitro enzyme activity by 43, 35, 21 %, respectively. Lithium at concentration of 5x10(-3) M could not either inhibit MAO-A or MAO-B in the mitochondrial fraction of rat brain.

Analgesia in phasic and tonic pain tests in a pharmacological model of autotomy.

Self-mutilation or self-injurious behaviour is a well known behavioural disorder in humans. The proposition that this behaviour in animals is a response to chronic pain of peripheral nerve injury has been met with controversy. In the present study a pharmacological model, which produces no sensory or motor loss was used to study how autotomy is related to pain. In a group of rats autotomy was induced by amphetamine in phenoxybenzamine and reserpine treated animals. The pain tests, both phasic and tonic were then performed. The results of this study showed that a total analgesia was produced in both phasic and tonic pain tests, in animals that exhibited autotomy. Injection of naloxone in these animals prevented autotomy. A correlation between autotomy and no pain is suggested in this pharmacological model of autotomy.

Evidence for presence of GABA-ergic receptor mediated dispersion in isolated scale melanophores of a carp, Cirrhinus mrigala Ham.

Effects of GABA-ergic agonists and antagonists were examined on the melanophores of a carp C. mrigala in vitro. GABA and baclofen both induced concentration - related dispersion in fish melanophores. Denervation of the melanophores by reserpine treatment potentiated the sensitivity of the melanophores to GABA. While denervation by cooling treatment inhibited the sensitivity of the melanophores to GABA, atropine, bicuculline and pentylenetetrazole all inhibited the dispersal responses of the melanophores induced by higher concentrations of GABA. 5-aminovaleric acid also significantly inhibited the dispersion of the melanophores induced either by GABA or baclofen. It is concluded that GABA-ergic agonist induced dispersal responses in C mrigala melanophores are mediated through specific GABA receptors. The presence of both GABAA and GABAB receptors in this fish melanophores has been indicated.

Serotonergic mechanism in imipramine induced antinociception in rat tail flick test.

Substantial evidence has accumulated that spinally projecting serotonergic neurons modulate nociception. However, the exact receptor subtypes that mediate the antinociceptive response of serotonin within the spinal cord continue to be a subject of debate. Therefore, we explored the effect of serotonergic system on imipramine induced antinociception by using 5-Hydroxytryptamine-3 (5HT3) receptor antagonist ondansetron and 5-Hydroxytryptamine-2 (5HT2) receptor antagonist mianserine, and depletion of brain 5-Hydroxytryptamine (5HT) with p-chlorophenyl alanine (PCPA). Male wistar strain rats were pretreated with either ondansetron (0.5 mg/kg, i.p.) or mianserine (1 mg/kg, i.p.). After 15 minutes, rats received injection of imipramine (10 mg/kg). Nociception was assessed by tail-flick method. Imipramine (2 mg, 5 mg, 10 mg, and 20 mg/kg) produce antinociceptive response in the dose dependent manner. Prior treatment with 5HT3 antagonist, Ondansetron and 5HT2 antagonist, mianserine reduce the antinociceptive response of imipramine. In PCPA treated rats imipramine (10 mg/kg) failed to produce antinociception. These results indicate that the 5HT plays an important role in imipramine induced antinociception.

Mudança no padrão biológico da migrânea com aura após a utilização da tetrabenazina: relato de caso / Change in the biologic pattern of the migraine with aura after the use of tetrabenazine: case report

A participação do sistema dopaminérgico na fisiopatologia da migrânea tem sido proposta a partir de recentes conquistas genéticas. Uma possível hipereatividade dos receptores dopaminérgicos DRD2 tornou as evidências mais contundentes neste sentido. Descrevemos paciente masculino, 31 anos, portador de distonia generalizada, secundária a hipóxia perinatal. Aos 16 anos, começou a ter crises de cefaléia que preenchiam os critérios para migrânea com aura. Três anos após tratamento da distônia com tetrabenazina, observou-se nítida redução da frequência, intensidade e duração das crises. Durante dois períodos, superiores a dois meses, a interrupção do tratamento com tetrabenazina induziu piora nas crises de migrânea. Apresentamos este relato como sendo a primeira descrição na literatura mostrando efeitos benéficos da tetrabenazina, um bloqueador dos receptores dopaminérgicos, sobre o comportamento da migrânea com aura.

The serotonin paradox: drug-receptor interaction in rat vas deferens

The contractile effect of serotonin was studied in rat vas deferens, in comparison with that of noradrenaline and tyramine, after reserpine treatment, surgical denervation, and transplantation to the colon. In reserpinized animals the effect of 5HT resembled that of tyramine, since it was strikingly reduced, in spite of a small residual effect, showing that in normal preparations the effects of 5HT and tyramine are predominantly duc to the release of endogenous noradrenaline. However, in denervated or transplanted vas deferens, in which the effect of tyramine is also abolished, the effect of 5HT was potentiated. It is suggested that after chronic, long lasting depletion of endogenous noradrenaline, there are alternate mechanisms that are generated to improve the contractile effect of 5HT, but not of tyramine. The nature of these mechanisms is still unknown.

Role of noradrenaline uptake inhibition and alpha-adrenoceptors in reperfusion ventricular arrhythmias in vivo and in vitro.

In view of the importance of sympathetic nervous system in the genesis of cardiac arrhythmias during reperfusion following coronary occlusion, the role of noradrenaline uptake inhibitor desipramine in the prevention of reperfusion arrhythmias was investigated in intact rabbit heart and isolated rat heart. For both the paradigms, ischaemia was produced by coronary artery ligation for 30 min followed by reperfusion for 60 min with drug administration at the time of reperfusion. Desipramine was used at three dose levels (0.2, 0.6 and 2.0 mg/kg) in the in vivo study while in vitro it was used at a concentration of 7 microM. Further, to investigate the status of adrenergic receptors during ischaemia and reperfusion, ischaemia was simulated by superfusing lactate physiological solution in isolated rabbit aortic strip preparation, which has well characterized alpha-receptors. Cumulative dose response curves (DRC) of selective alpha 1 agonist, phenylepherine (PE) were recorded during normal, ischaemic and reperfused conditions. Desipramine showed dose dependent anti-arrhythmic effect in vivo as well as in vitro. In intact heart studies desipramine offered protection against reperfusion arrhythmias in a dose related manner i.e. 50, 67.5 and 100% whereas in isolated studies, 50% protection was observed in the overall incidence of arrhythmias. DRC of PE shifted towards right during both ischaemia and reperfusion with a significant elevation of maximal response only during reperfusion.