Effect of the carbamate [physostigmine] on the activity of nitric oxide synthase in different parts of rat brain [invivo studies]

Physostigmine [eserine] is the methyl carbamic ester of phenolic trimethyl ammonium compound. It is a powerful inhibitor of acetylcholinesterase enzyme activity and used in some therapeutic preparation. In this work, experiments were carried out in-vivo to study the intraperitoneal [i.p.] infusion of eserine on the activity of nitric oxide synthase [NOS] enzyme, obtained from whole and five different parts of rat brain, namely: basal ganglia, frontal cortex medulla oblongata, pons, and cerebellum. In this work ,two experiments were carried Experiment A: to study the dose dependence of i.p. infusion of eserine on NOS activity. Experiment B: to study the time dependence post-infusion of constant dose of eserine [the dose which caused 50% inhibition of the enzyme activity: 150]. The results showed that the "inhibition of the enzyme occurred in each part studied, and the inhibition increased with increasing the infused dose of eserine, and the time post i.p. infusion, i.e., the inhibition is dose and time dependent. The highest inhibition occurred in the pons and medulla oblongata extracts; these parts are responsible for the reflex centers of cough and vital centers

Vias dopaminérgicas e somatostatinérgicas diminuem o TSH sérico em ratos portadores de carcinoma mamário walker-256 / Dopaminergic and somatostatinergic pathways decrease serum thyrotropin in rats bearing the 256-walker mammary carcinoma

A funcão do eixo hipotálamo-hipófise-tireóide em animais portadores da "síndrome do T3 baixo", foi estudada em ratos implantados com o tumor de Walker-256. Ratos machos adultos foram injetados com 1 x 106 células tumorais viáveis, por via SC, e sacrificados após 10 dias. A intensidade da síndrome guardou relacão positiva com o tamanho do tumor desenvolvido. Houve diminuicão da atividade tireoideana documentada pela diminuicão da área nuclear das células foliculares, das concentracões plasmáticas do T4, da rTg e da captacão do 131I. Mesmo o implante SC de um pellet de TSH de liberacão lenta causou menor estimulacão tireoideana, avaliada após 2 e 24h nos ratos com tumor. A secrecão do rTSH avaliada através da administracão IV de TRH mostrou-se significativamente diminuída nestas condicões, indicando aumento do tônus inibidor hipotalâmico sobre a secrecão deste hormônio. A participacão de outros neuro-mediadores hipotalâmicos foi verificada através da administracão prévia de metoclopramida e/ou fisostigmina, com ou sem estímulo subseqüente pelo TRH. Nos animais tratados com metoclopramida, os valores do rTSH aumentaram significativamente, assim como a resposta ao estímulo de secrecão pelo TRH. A fisostigmina mostrou-se mais eficiente na mediacão da resposta de secrecão do rTSH, bem como na resposta ao estímulo de secrecão pelo TRH. A administracão concomitante dos dois fármacos, seguida do estímulo pelo TRH, normalizou a secrecão do rTSH. Conclui-se que, além das alteracões conhecidas do metabolismo das iodotironinas, a secrecão de TSH encontra-se diminuída nos animais portadores de tumor de Walker-256, sugerindo diminuicão global do tônus tireoideano.

Sildenafil improves acquisition and retention of memory in mice.

Sildenafil (Viagra) has been introduced recently in market to correct male impotency and has gained immense popularity for its dramatic effects all over the world. The present study was designed to investigate the effect of sildenafil on learning and memory in mice using elevated plus maze. A total of XV groups of animals were employed in the present study. Central cholinergic pathways play a crucial role in learning and memory processes. Physostigmine, an anticholinesterase agent (0.5 mg, 1.0 mg kg(-1), i.p) was employed for its memory enhancing property and alprazolam a benzodiazepine receptor agonist served as a memory-impairing agent. In the present study, alprazolam produced anterograde amnesia (at 0.5 mg kg(-1), i.p) and retrograde amnesia (at 0.25 mg, 0.5 mg, 0.75 mg kg(-1), i.p.) in separate groups of animals. Caffeine at 5 mg, 10 mg and 20 mg kg(-1), i.p. (an established psychostimulant) did not show any significant change in learning and memory of mice. Sildenafil (at 8 mg kg(-1), i.p.) administered 30 minutes prior to training on first day produced a marginal decrease in transfer latency time on first day; whereas, sildenafil (at 2 mg, 4 mg, 8 mg kg(-1), i.p.) administered immediately after training on first day produced a dose-dependent improvement of memory in mice. However, further studies need to be carried out to elucidate the underlying mechanism of sildenafil as a memory enhancer.

Indirect excitatory actions of histamine on isolated chicken oesophagus.

The histamine-induced contraction on chicken oesophagus was antagonised non-competitively by atropine, hexamethonium, cocaine, methysergide, indomethacin, theophylline and verapamil. Physostigmine slightly potentiated the excitatory action of histamine. These results indicate that histamine excreted its excitatory action by involving a number of mechanisms as suggested in guinea pig oesophagus.

Latency of memory consolidation induced in mice by piracetam, a nootropic agent.

Piracetam (PIR), a cyclic GABA derivative, is the prototype of a new class of psychoactive drugs, the nootropic agents, which improve learning acquisition and the retention of the learning as memory. It was proposed that nootropics act on processes essentially involved in information storage, thus facilitating memory. This property can best be investigated by drug administration after the learning trial and assessing subsequent retention performance. The present study was designed to evaluate the effective time period of memory consolidation, induced by piracetam, by assessing the retention of a learned task in two behavioural paradigms, following administration of the drug after learning acquisition. Physostigmine was used as the standard drug because of its well established facilitation of memory storage. PIR (250 and 500 mg/kg, ip) and physostigmine (0.05 mg/kg, ip) were administered in different groups of mice 5 min, 1, 2, 4, 8, 12 and 24 hr after learning acquistion of two passive avoidance tasks and the retention performance was evaluated 3 days later. The results indicate that, while physostigmine induced significant memory consolidation when administered up to 2 hr after learning acquisition, PIR induced retention of learning beyond this period. Thus, the highest effective post-trial interval for the lower and higher dose of the drug was 8 and 12 hr, respectively, in both the test paradigms. The results confirm that nootropics, like piracetam, are capable of memory consolidation, as assessed by retention of learning, even after intervals of 8 to 12 hr between learning and drug treatment.

Influence of pretreatment of carbamates on dynamic pulmonary mechanics in rats exposed to sarin aerosols.

The effect of pretreatment of two carbamates, pyridostigmine and physostigmine on dynamic pulmonary mechanics has been studied in rats exposed to sarin aerosols. Sign-free dose of pyridostigmine (0.075 mg/kg, i.m.) or physostigmine (0.1 mg/kg, i.m.) did not significantly alter the parameters of the dynamic pulmonary mechanics 20 min after treatment. However, sarin (51.2 mg/m3, for 15 min) depressed the respiratory rate, air flow and minute volume and enhanced the transthoracic pressure and tidal volume. Pretreatment with carbamates 20 min prior to sarin exposure significantly modified or counteracted the above induced changes. It is concluded that the protective effect of carbamates is mainly due to the correction of respiratory changes caused by sarin aerosols in rats.

Estudo dos movimentos espontâneos e sob efeitos farmacológicos de segmentos isolados da junçäo duodeno-jejunal de rato / Spontaneous and drug-induced movements of isolated segments of the duodenojejunal junction of rat

Estudou-se, "in vitro", a motilidade espontânea e sob efeito farmacológico da junçäo duodenojejunal de ratos. Tomou-se três segmentos: pré, no nível e após a junçäo. Os registros foram feitos em quimógrafo com papel enfumaçado. A acetilcolina e fisostigmina diminuíram as amplitudes de contraçöes nos três segmentos, bem como a noradrenalina e procaína. A freqüência das contraçöes espontâneas apresentou um gradiente decrescente no sentido crânio-caudal, observado tambem sob o efeito da noradrenalina. Sob o efeito acetilcolina e fisostigmina elas se igualaram. Näo houve diferença quanto ao tipo de ondas (I, II e III), sendo mais frequüente a onda I. Elas näo se alteraram sob a açäo da acetilcolina e noradrenalina, e a fisostigmina alterou as características das ondas. O efeito da procaína sobre as ondas foi marcante, diferenciando, nitidamente, o segmento pré da transiçäo duodenojejunal. O tono foi igual nos três segmentos. A acetilcolina diferenciou o segmento pré do pós-junçäo duodenopejunal. A noradrenalina e a procaina diminuiram o tono e a fisostigmina aumentou-o igualmente nos três segmentos

Effects of carbamates on the hemodynamic parameterns of rats treated or not with (alpha) - Pyridylaldoxime methylsulfomethylate (P2S)

O objetivo da presente investigaçäo foi determinar os efeitos de doses tóxicas de agentes anticolinesterasicos carbamatos, fisostigmina e carbaril, na pressäo arterial e freqüência cardíaca de ratos, bem como a açäo protetora do reativador de colinesterase, a pralidoxima, contra estes efeitos. A acetilcolina injetada intravenosamente, em ratos, causou uma imediata queda dose-dependente na Pressäo Arterial Média (PAM), seguida por um aumento na PAM que apresentava duraçäo maior que a queda. Houve também uma queda na Freqüência Cardíaca (F.C). Injeçäo intravenosa de carbaril em rato normal causou uma queda na PAM dentro de 5 segundos, seguida pelo aumento significante na mesma em relaçäo ao valor do controle, 5 minutos após a injeçäo Carbaril näo provocou nenhum efeito na F.C. Quando o carbaril foi precedido pela injeçäo de pralidoxima, as alteraçöes na PAM foram similares àquelas observadas após a injeçäo de carbaril isoladamente, porém a F.C. diminuiu de maneira significante nos grupos que receberam doses maiores. Fisostigma injetada intravenosamente em ratos normais näo apresentou efeito imediato (5 segundos) na PAM, porém ocorreu um aumento significante na PAM 5 minutos após a injeçäo. Nenhuma alteraçäo significante ocorreu na F.C. Em animais previamente tratados com pralicoxima, a fisostigmina causou uma queda imediata na PAM que foi seguida por um aumento significante em relaçäo ao controle, 5 minutos após a injeçäo. Uma queda na F.C. também ocorreu. Administraçäo prévia de pralitoxima potenciou os efeitos cardiovasculares causados pela fisostigmina, porém näo os efeitos do carbaril.

Participation of nucleous raphe obscurus in the control of sympathetic activity in the anesthetized rat

The medullary raphe are involved in the control of sympathetic activity during desynchonized sleep and in the modulation of nocicepotive sensory inpts. To determine the particpation cholinergic and opiate mechanisms in the control of sympathetic activity, we microinjected eserine, morphine and naloxone into the nucleus raphe obscurus (NRO) of urethane-anesthetized rats. Arterial blood pressure (BP) and renal nerve activity (RN) were recorded. Eserine and morphine induced significant reductions of RN and BP, while naloxone had no effect. It is suggested that cholinergic and opiate mechanisms particpate in the control of sympathetic activity by th NRO

Effect of beta-adrenoceptor antagonists and some related drugs on maximal electroshock seizures in mice.

(+/-) Propranolol (1-50 mg/kg), (+) propranolol (50 mg/kg) and pindolol (10-50 mg/kg) exhibited significant protective effects against MES (maximum electroshock seizures), whereas, timolol (1 mg/kg), the propranolol analog, UM-272 (1 and 10 mg/kg), and the beta-agonist, terbutaline (1 and 10 mg/kg) were ineffective. Cholinergic agents, physostigmine (0.01-1.0 mg/kg), and atropine (1 and 10 mg/kg), the serotonin antagonist, cyproheptadine (0.05 mg/kg), and the prostaglandin synthesis inhibitor, indomethacin (10 mg/kg), were also without effect on the MES extensor phase. Further, pretreatment of mice with terbutaline, atropine, cyproheptadine or indomethacin did not influence the anti-MES effect of propranolol to any significant extent. The results indicate that the observed anticonvulsant effects of beta-adrenoceptor antagonists are unrelated to noradrenergic or other central neurotransmitter systems and that a non-specific mechanism, probably a membrane stabilizing effect is involved.

Effects of physostigmine on the activity of medullary raphe neurons in anesthetized rats

Medullary raphe neurons are involved in the control of sympathetic activity during desynchronized sleep. To determine if cholinergic simulation of these sites has any effect on raphe unit activity, we administered physostigmine to urethane'anesthetized rats. Most of the neurons (68%) were excited by physostigmine, suggesting the existence of cholinergic synapses which are excitatory for the majority of medullary raphe neurons

Effects of metoclopramide on spontaneous and pharmacologically-induced yawning in the rat

La metoclopramida (MCP) ha sido caracterizada por Alender et al. (1980) como un fármaco que tiene una acción 4 a 5 veces mayor sobre los respcetores dopaminérgicos presinápticos (autorreceptores) que sobre las postsinápticos. En este trabajo se estudia su acción sobre el bostezo espontáneo o inducido por fisostigmina (0,10 mgKg, i.p.) y apomorfina (0.05 mgKg, s.c.) en ratas machos Sprague Dawley de dos a tres meses de edad. Los efectos de la MCP se exploraron en el rango de 0.3 a 1.0 mgKg, rango en el cual el fármaco es selectivamente activo sobre los autoreceptores. Los animales se inyectaron, i.p., 15 minutos antes de la observación conductual. Se encontraron reducciones de la frecuencia del bostezo proporcionales a las dosis utilizadas, obteniéndose con la dosis máxima (1.0 mgKg), un decremento de 90% y 60%, respectivamente, en el bostezo espontáneo y el inducido con fármacos. Estos resultados son compatibles con la hipótesis de que los autorreceptores presinápticos dopaminérgicos desempeñan un papel fisiológico en la regulación del bostezo

Effect of physostigmine and atropine on the single-trial passive avoidance response in rats.

Rats received a single training trial on an inhibitory avoidance (passive avoidance) task and retention trials 24 hr (R-I) and 48 hr (R-II) later, in a special two-chambered apparatus, and the mean step-through latency was determined. The animals were given the drug, either pre-trial, pre-trial plus pre-retention, pre-retention or post-trial. Physostigmine (0.1 mg/kg, ip) and atropine (6.0 mg/kg, ip) had no effect on learning, but they adversely affected retention, particularly at 24 hr. The effect seems to involve central cholinergic mechanisms of retention.