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S K Kulkarni

Publications and source records attributed to S K Kulkarni.

At least 181 records · Page 10Linked to original sources
PubMed1989

GABAergic agents-induced antinociceptive effect in mice.

The effect of GABA agonists, namely gamma aminobutyric acid, muscimol, sodium valproate and baclofen was studied on radiant heat-induced nociception in mice. All of the drugs, with the exception of sodium valproate, enhanced the reaction time to radiant heat as effect per se. Concomitant administration of any of these agents with morphine showed a potentiation of morphine-induced analgesia. The GABA antagonists bicuculline and picrotoxin failed to reverse the antinociceptive effect; paradoxically both these agents showed antinociceptive effect per se and also enhanced the response due to morphine.

Analgesics↗
PubMed1989

GABAergic agents and clonidine attenuate footshock-induced aggression in mice.

The effects of gamma aminobutyric acid (GABA), baclofen, and clonidine was studied on footshock-induced aggression in mice. A lower dose (200 mg/kg) of GABA enhanced the aggressive score, while at a higher dose (400 mg/kg) it attenuated the aggressive behavior, the latter effect being reversed both by bicuculline and picrotoxin (PTX). Clonidine (0.5 and 1 mg/kg) enhanced the aggressive score, and the effect of clonidine was reversed by idazoxan. GABA (400 mg/kg) and clonidine (1 mg/kg) significantly reduced the aggressive score in reserpinized mice. Baclofen (5 mg/kg) showed no effect per se in either reserpinized or non-reserpinized mice. On concomitant administration of clonidine (0.5 mg/kg) with a subeffective dose of either GABA, baclofen, or diazepam, there was significant reduction in the aggressive score. A modulatory role of GABAergic and noradrenergic systems in footshock-induced aggression is suggested.

Aggression↗
PubMed1988

Molecular interactions of ethanol with GABAergic system and potential of RO15-4513 as an ethanol antagonist.

The behavioral and biochemical effects of ethanol in man and animals have been investigated for a long time. A role of catecholamines in the central stimulatory action and during withdrawal has been envisaged, but more recent observations have revealed the involvement of inhibitory synaptic transmitter, GABA, in the actions of ethanol. Ethanol-induced motor incoordination, hypnosedation, antianxiety, and anticonvulsant actions are reported to be GABA-mediated. Involvement of the GABA system has been implicated in ethanol withdrawal-induced seizures in animals. More direct evidences using Cl- influx studies in synaptoneurosomes and spinal neuronal culture studies confirm such a mode of action of ethanol, probably influencing the chloride channel modulation at the GABA-benzodiazepine receptor ionophore complex. RO15-4513 (ethyl-8-azido-5,6-dihydro-5-methyl-6-Oxo-4H-imidazo [1,5-alpha], [1,4] benzodiazepine-3-carboxylate), a novel imidazobenzodiazepine, an analogue of the classical benzodiazepine antagonist is reported to possess alcohol antagonistic properties. RO15-4513 reverses both the behavioral and biochemical effects of ethanol, including the action of GABA-induced Cl- fluxes. But its potential clinical application may be restricted due to its inverse agonistic property. The present review focuses on the GABA-linked behavioral and biochemical actions of ethanol and discusses the potential of RO15-4513 as an alcohol antagonist.

Animals↗
PubMed1988

GABAergic, dopaminergic and cholinergic interaction in tremorine-induced tremors in mice.

Antitremor effects of systemically administered GABA agonists (GABA and sodium valproate) and GABA antagonists (bicuculline and picrotoxin) were studied in mice against tremorine-induced tremors. None of the GABA agonists were found to possess any antitremor effect, whereas GABA antagonists were found to possess protective effect against tremorine-induced tremors. Simultaneous administration of GABA agonists with sub-effective doses of anticholinergic agent (scopolamine) did not potentiate antitremor effect of scopolamine, whereas GABA antagonists and effective doses of scopolamine when administered simultaneously resulted in antagonism of protective effect of scopolamine. Similarly, when GABA agonists and sub-effective doses of dopaminergic agent, bromocriptine, were administered simultaneously, the protective effect of bromocriptine was potentiated. When GABA antagonists and effective doses of bromocriptine were administered simultaneously, the protective effect of bromocriptine was antagonized. The modification of the protective effect of anticholinergic and dopaminergic agents by GABAergic agents has been explained on the basis of neurotransmitter interaction.

Animals↗
PubMed1988

Anticatatonic effect of venoruton.

The protective effect of venoruton O-(beta-hydroxy-ethyl) rutoside, HR was investigated against drug induced catatonia in rats. Perphenazine, haloperidol, reserpine and meperidine produced frank catalepsy in rats. The cataleptic effect of these neuroleptics was significantly attenuated when the animals were pretreated with venoruton. The protective effect of venoruton is speculated to be due to its inhibitory action on superoxide formation and free radicals are considered to have a role in the neurotoxicity caused by the above agents.

Animals↗
PubMed1988

Studies on the neuropsychopharmacological profile of fengabine (SL 79229) in mice.

The effect of fengabine (a novel benzylidene derivative) on neuropsychopharmacological parameters was investigated in mice. On acute systemic administration, it showed modulatory effects on 1) forced swimming-induced immobility, 2) foot shock-induced aggression, 3) electromaximal shock-induced convulsion, 4) radiant heat-induced nociception and 5) locomotor activity. However, it has no effect on the muscle strength of the animal. The GABAA receptor antagonists reversed its effects on forced swimming-induced immobility and foot shock-induced aggression, implicating a GABAergic involvement in its mechanism of action. But these antagonists failed to reverse its potentiating effect on morphine antinociception, suggesting a possible interaction of the drug with opioid receptors. A potential clinical usefulness of the drug and of GABA agonists in general is commented upon.

Aggression↗
PubMed1987

Modulatory effect of alpha 2 adrenoceptor agonists on Ro 5-4864-induced convulsions in rats and mice.

The protective effect of various alpha 2 adrenoceptor agonists such as clonidine, guanfacine, B-HT 920 and ICI 106270 was investigated against Ro 5-4864-induced convulsions in mice and rats. Clonidine and ICI 106270 exhibited a profound anticonvulsant effect while equivalent doses of guanfacine and B-HT 920 were less effective. The anticonvulsant effect of clonidine and ICI 106270 was reversed by pretreatment with yohimbine or idazoxan, indicating the involvement of alpha 2 adrenoceptors in their protective effect. Diazepam, clonazepam, CL 218, 872 and pentobarbitone exhibited a different profile of protective action, as these agents protected the animals from apparent mortality as compared to clonidine and ICI 106270 which prolonged the latencies of jerk and convulsion. Modulatory effects of alpha 2 adrenoceptors in central GABA function and multiple sites for Ro 5-4864-induced seizures are explained.

Animals↗
PubMed1987

Involvement of central type benzodiazepine and GABAA receptor in the protective effect of benzodiazepines in stress-induced gastric ulcers in rats.

Various benzodiazepines (BZs) were studied for ulcer protective effect in immobilization stress-induced gastric ulcers in rats. Central type BZ receptor agonists such as clonazepam, chlorodiazepoxide and diazepam shared marked antiulcer effect. The ulcer protective action of these agents was reversed by pretreatment with Ro 15-1788, a central BZ receptor antagonist. However, peripheral BZ receptor binding agent Ro 5-4864 and BZ-micromolar binding agent phenytoin, failed to show any antiulcer effect. Pretreatment with bicuculline also reversed the ulcer protective action of central type BZ receptor agonists. A bicuculline sensitive potentiation was observed in the ulcer protective effect of central BZ receptor agonist, when a subeffective dose was combined with muscimol, a specific GABAA agonist. But no such potentiation was seen with baclofen, a GABAB agonist. These data imply an interaction of central type BZ receptor with GABAA subtype receptor in the ulcer protective effect of benzodiazepines in rats.

Animals↗
PubMed1987

Evidence of beta-adrenergic involvement in forced swimming-induced behavioural despair of mice.

Modulation of forced swimming-induced immobility by beta-adrenoceptor activation was investigated in mice. Isoprenaline prolonged the immobility duration of mice in a dose-related manner when the animals were forced to swim for 6 min periods. On the other hand, salbutamol (a beta 2-agonist) reduced the immobility duration of mice. Pretreatment with propranolol (1,2,4,8 and 16 mg/kg, ip), atenolol (10 mg/kg, ip) and metoprolol (10 mg/kg, ip) antagonized the immobility-enhancing effect of isoprenaline. Chronic administration (10 mg/kg/day) for 8 days of propranolol and imipramine protected the animals from isoprenaline-evoked prolongation of immobility. These findings suggest that central beta 1- and beta 2-subtypes of adrenoceptors may be acting in opposite directions to modify the immobility duration of mice. Activation of central beta 1-adrenoceptors may lead to enhanced behavioural despair, whereas a reverse effect may be observed on beta 2-adrenoceptor activation.

Animals↗
PubMed1987

Naloxone-sensitive and GABAA receptor mediated analgesic response of benzodiazepines in mice.

Various benzodiazepines (BZs) were investigated for their analgesic effect by the tail-flick method in mice. Central type BZ-receptor agonists such as clonazepam, chlordiazepoxide and diazepam showed analgesia while the peripheral BZ-receptor binding agent, Ro 5-4864, and the BZ micromolar binding agent phenytoin, failed to show any effect. Other BZs, such as lorazepam and nitrazepam, were ineffective in producing analgesia. Pretreatment with naloxone antagonized the analgesic effect of central type BZ-receptor agonists. Similarly, pretreatment with Ro 15-1788, a central BZ-receptor antagonist, also blocked the analgesic effect. When the involvement of the GABAergic system in the analgesic response of BZ agonists was investigated, a potentiation of BZ action was seen as a combination of a subeffective dose of clonazepam with a subanalgesic dose of muscimol, a specific GABAA agonist, showed an enhanced effect. Moreover, pretreatment with GABAergic substances like pentobarbitone also showed a facilitatory effect on BZ-induced analgesia. On the other hand, a combination of clonazepam with baclofen, a specific GABAB agonist, failed to show any synergistic effect. The analgesic effect of central type BZ-receptor agonists was found to be bicuculline reversible. It is concluded that GABAA receptor activation has a modulatory role in the naloxone sensitive analgesic effect of central type BZ-receptor agonists.

Analgesics↗
PubMed1987

Clonidine in alcohol withdrawal: a clinical report.

Potential of clonidine in the treatment of alcohol withdrawal reactions was investigated. Clonidine was found to be remarkably effective in alleviating various alcohol abstinence signs in a chronic alcoholic. The usefulness of clonidine and related alpha 2-agonists in the treatment of alcohol withdrawal states is discussed.

Adult↗
PubMed1987

Antagonism by naloxone of anti-tremorine effect of bromocriptine in mice.

Effects of the opioid antagonist naloxone (10 mg/kg) and its interaction with anticholinergic (scopolamine) and dopaminergic (bromocriptine) agents against tremorine-induced tremors was studied. Naloxone (10 mg/kg) per se gave significant protection and significantly potentiated the protective effect of scopolamine against tremorine-induced tremors at 5 min only. When naloxone and subeffective dose of bromocriptine (2 mg/kg) were administered simultaneously, instead of protection, an enhancement of tremorogenic activity was seen. Although the exact mechanism of this drug interaction is far from clear, a multireceptor involvement (i.e. opioid, dopaminergic and cholinergic type) in the modulation of tremorine-induced tremors in mice has been speculated.

Animals↗
PubMed1987

Studies on meperidine-induced catalepsy in mice.

Anticataleptic effect of different pharmacological agents was studied against meperidine-induced (50 mg/kg i.p.) catalepsy in mice. MAO (A and B) inhibitors, alpha 2-agonists in addition to dopaminergic, GABAergic and serotoninergic agents, were found to be effective in attenuating the cataleptic symptoms. However, naloxone, an opiate antagonist, failed to reverse meperidine-induced akinesia and rigidity. Clorgyline, a specific MAO-A inhibitor, was found to be more potent than the MAO-B inhibitor selegiline.

Animals↗