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Biomedical subjects

S K Kulkarni

Publications and source records attributed to S K Kulkarni.

At least 199 records · Page 11Linked to original sources
PubMed1986

Reversal by alpha-2 agonists of diazepam withdrawal hyperactivity in rats.

Rats were made diazepam dependent by chronic treatment with daily injections of the drug, 20 mg/kg, IP, for 3 weeks. On abrupt termination of the drug, the animals showed withdrawal hyperactivity which was indicated by increased horizontal locomotion and vertical activity, and diarrhoea. The peak effect was seen 3 days after the withdrawal of diazepam. Effects of various alpha 2 agonists, clonidine, guanfacine and B-HT 920, were studied on the diazepam withdrawal phenomena. Clonidine (100 micrograms/kg, IP) given twice a day at an interval of 12 h prevented both withdrawal-induced hyperactivity and diarrhoea. On the contrary, equimolar doses of guanfacine and B-HT 920 failed to reverse withdrawal-induced hyperactivity but attenuated the effect of diarrhoea. However, higher doses (500 micrograms/kg, IP) of guanfacine and B-HT 920 given twice a day at 12-h intervals were found to be effective. Pretreatment with yohimbine (1.5 mg/kg, IP) reversed the protective effect of clonidine, indicating the involvement of alpha 2 receptors in the action of clonidine.

Adrenergic alpha-Agonists↗
PubMed1986

Clonidine--induced behavioural despair in mice: reversal by antidepressants.

The effects of various alpha 2 adrenoceptor agonists on forced swimming-induced despair behaviour were studied in mice. Clonidine, B-HT 920 and guanfacine significantly prolonged the total immobility duration. Clonidine-induced behavioural despair was antagonized by prior treatment with yohimbine. The tricyclic antidepressants imipramine, desipramine, trimipramine, amitriptyline, nortriptyline and doxepin, the MAO inhibitor tranylcypromine, and the antimanic agent lithium reversed clonidine-induced behavioural despair. Chronic treatment with imipramine evoked more pronounced reversal as compared to acute treatment. Amphetamine, a psychostimulant, inhibited clonidine-induced enhancement of immobility duration but diazepam, a skeletal muscle relaxant was without any effect. On the other hand, adenosine showed potentiation of the submaximal response of clonidine. These observations suggest that clonidine-induced behavioural despair is probably mediated through its presynaptic action on alpha 2 adrenoceptors, resulting in reduced central noradrenergic outflow. The present data proposes a simple test system to induce depression-like syndrome in animals, sensitive to antidepressant therapy.

Animals↗
PubMed1986

Studies with alpha 2-adrenoceptor agonists and alcohol abstinence syndrome in rats.

Various alpha 2-adrenoceptor agonists were assessed for their effects on alcohol abstinence syndrome in rats. In the first experimental model, groups of Wistar rats were made alcohol dependent by feeding alcohol together with sweetened milk for 15 days. The volume of fluid intake was measured every 12 h to determine daily ethanol consumption. Abstinence signs following abrupt alcohol withdrawal were observed in control as well as test groups receiving various alpha 2-adrenoceptor agonists. Clonidine, guanfacine and B-HT 920, in equimolar concentration (0.5 microM/kg), effectively attenuated the various abstinence signs, which developed after alcohol withdrawal. In the other experimental model, rats were subjected to cold water immersion to induce wet shakes. The inhibitory action of alpha 2-adrenoceptor agonists was assessed in this test model. Clonidine, guanfacine and B-HT 920 markedly suppressed the cold water immersion-induced wet shakes and pretreatment with yohimbine (0.1 and 2.0 microM/kg) reversed this inhibitory effect. The present data reveal the possible therapeutic potential of alpha 2-adrenoceptor agonists in alleviating alcohol abstinence syndrome, and suggest that the resultant reduced noradrenergic activity may be responsible for the beneficial action.

Adrenergic alpha-Agonists↗
PubMed1986

Anticatatonic effect of clonidine: its interaction with dopaminergic, anticholinergic and GABA-ergic drugs.

Anticatatonic effects of systemic (50 micrograms/kg, i.p.) and intracerebroventricularly (5 micrograms/10 microliters/rat) administered clonidine was studied in rats against perphenazine-induced catatonia. Clonidine was found to possess anticatatonic actions in rats as it significantly blocked perphenazine-induced catatonia. When clonidine was administered simultaneously with dopaminergic (dopamine, bromocriptine), anticholinergic (scopolamine, diphenhydramine) and GABA-ergic (GABA, muscimol) agents there was a potentiation of the anticatatonic effect. However, clonidine-anticholinergic combination showed a better protective response as compared to clonidine-dopaminergic combination. The protective effect of clonidine and its modification by anticholinergic agents has been explained on the basis of direct central adrenergic as well as central anticholinergic actions of clonidine. Although higher dose of GABA-ergic agents was not studied due to toxicity, the combined effect of clonidine and GABA-ergic agents has been explained on neurotransmitter interactions.

Animals↗
PubMed1986

Apparent pA2 estimation of benzodiazepine receptor antagonists.

The in vivo equivalent pA2 values for benzodiazepine (BZ) antagonists Ro15-1788 and CGS 8216 were estimated using diazepam as agonist. ED50 value of diazepam was established against pentylenetetrazole-induced seizures in rats. This value was raised by pretreatment with BZ antagonists Ro15-1788 and CGS 8216, in a dose-dependent manner. The apparent pA2 values for Ro15-1788-diazepam pair and CGS 8216-diazepam pair were found to be 5.28 and 5.48, respectively, which indicates almost equal antagonistic potency at the BZ receptor in reversing the protective effect of diazepam against pentylenetetrazole seizures in rats.

Animals↗
PubMed1986

MPTP: a pharmacological tool to study parkinsonism.

MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is reported to selectively degenerate dopaminergic cells of the zona compacta of the substantia nigra and produce Parkinson's-like symptoms in man and animals. Although the exact mechanism of its neurotoxicity is not well defined, a major metabolite MPP+ may be responsible for the ultimate neuron toxicity. Several classes of drugs useful in Parkinson's disease are effective in reversing MPTP-induced neurotoxicity. Future pharmacological studies on the compound may unlock some of the mysteries of the age old disease, parkinsonism.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1986

Modification by clonidine of harmine-induced tremors in mice: involvement of serotoninergic system.

Clonidine exhibited a dose-dependent protection against harmine-induced tremors in mice. This protective effect was not completely blocked by pretreatment with yohimbine. The serotoninergic (5-HT) agonist quipazine and the uptake inhibitor fluoxetine completely antagonized this effect. On the other hand, the 5-HT antagonist cyproheptadine potentiated the protective effect of sub-effective doses of clonidine. These observations suggest a serotonin-mediated action of clonidine in its antitremor action against harmine-induced tremors.

Alkaloids↗
PubMed1986

Anti-inflammatory actions of clonidine, guanfacine and B-HT 920 against various inflammagen-induced acute paw oedema in rats.

Clonidine (0.1-1.0 mg/kg, i.p.) exhibited anti-inflammatory activity in carrageenan-, formalin-, 5-HT- and histamine-induced paw oedema in rats. Similarly, other two alpha 2-adrenoceptor agonists, guanfacine and B-HT 920, also displayed an anti-inflammatory action in these models. The anti-inflammatory effect of all the three alpha 2-adrenoceptor agonists was reversed by yohimbine. However, prazosin failed to block the anti-inflammatory effect of clonidine. Intracerebroventricularly administered clonidine had a delayed onset of anti-inflammatory action, starting only from 60 min post carrageenan administration. This was in contrast to the systemically administered clonidine which was effective against both phases of carrageenan-induced oedema. On the other hand, irrespective of the route of administration, i.e. peripheral or central, guanfacine and B-HT 920 were effective against the early as well as against the delayed phases of the inflammatory reaction. The studies suggest that it is not the imidazoline moiety but the activation of alpha 2-adrenoceptors which is essential for the anti-inflammatory action of these agents.

Animals↗
PubMed1986

Yohimbine potentiates the anticataleptic action of clonidine against perphenazine-induced catalepsy in rats.

The modulatory role of clonidine and yohimbine on the perphenazine-induced catalepsy was studied in rats. Perphenazine (5 mg/kg) produced severe catalepsy which lasted for more than 4 hr. Clonidine (50 micrograms/kg), an alpha 2-agonist, pretreatment offered protection against perphenazine-induced catalepsy. On the other hand yohimbine (5 mg/kg), an alpha 2-antagonist, pretreatment not only showed per se protective action but also potentiated the effects of clonidine against perphenazine-induced catalepsy. Yohimbine also potentiated the protective action of quipazine, a serotonin agonist. The protective effect of yohimbine is explained on the basis of its serotoninergic action.

Animals↗
PubMed1985

Purine nucleoside--mediated immobility in mice: reversal by antidepressants.

In the forced swimming-induced immobility (despair) test model, adenosine, and 2-chloroadenosine treatment prolonged the immobilization period in mice. Dipyridamole, which is known to inhibit adenosine uptake, potentiated the adenosine effect. The purinoceptor antagonists caffeine and theophylline blocked purine nucleoside-induced enhancement of immobilization. Tricyclic antidepressants such as imipramine and desipramine, the MAO inhibitor tranylcypromine, and amphetamine, a psychostimulant, reversed purine nucleoside-induced immobility. On the other hand, quipazine, fluoxetine, and amitriptyline failed to reverse purine nucleosides-induced prolongation of immobility. None of the antidepressants in the doses investigated had any effect by themselves. Reserpine also prolonged forced swimming-induced immobility in mice. The antidepressants fluoxetine and quipazine, but not methylxanthine pretreatment, reversed reserpine-induced immobility in this test model. These results indicate that adenosine and 2-chloroadenosine probably reduce norepinephrine outflow through their action on presynaptic purinoceptors on noradrenergic neurons and thereby cause prolongation of immobility in animals.

2-Chloroadenosine↗
PubMed1985

Effect of alpha2 agonists clonidine, guanfacine and B-HT 920 on gastric acid secretion and ulcers in rats.

The antisecretory and gastric ulcer protective effects of clonidine were studied in four different experimental models in rats. The effects were compared with two other alpha2 agonists guanfacine and B-HT 920 at equimolar dose basis. Clonidine (0.05-1 mg/kg) produced antisecretory effect at all doses but the maximum effect was noticed at 0.1 mg/kg. Its ulcer protective effect against immobilization stress-induced ulcers was comparable to diazepam but was not completely reversed by Ro 15-1788, a benzodiazepine antagonist. Clonidine showed an inhibitory response on basal gastric secretion in the continuous perfusion technique. It also reversed the effects of systemically administered indomethacin on gastric acid secretion and ulcers. Guanfacine produced a biphasic response on basal gastric secretion. The excitatory response was prolonged by bilateral vagotomy and inhibited by cimetidine treatment. Tachyphylaxis was observed in its excitatory response. It also showed inhibitory effects on pyloric ligation and indomethacin-induced gastric acid secretion. While B-HT 920 shared the antisecretory effects of clonidine and guanfacine in pyloric ligation, stress and drug-induced gastric secretion and ulcer protection, it had little or no effect on basal secretion in the continuous perfusion of the stomach. Since yohimbine was able to reverse the inhibitory effects of alpha2 agonists, the antisecretory effect of these agents predominantly involved the action on alpha2 adrenoceptors.

Adrenergic alpha-Agonists↗
PubMed1985

Apparent pA2 estimates for an antinociceptive receptor.

The involvement of alpha 2-adrenoceptors in antinociception was investigated and apparent pA2 values determined using the tail flick technique in mice. Among various alpha 2-adrenoceptor agonists employed (viz. clonidine, guanfacine and B-HT 920) only clonidine exhibited antinociception in a dose-dependent manner, an effect analogous to morphine. B-HT 920 and guanfacine failed to show increased antinociception, with corresponding increase in concentration. Yohimbine (1.28 X 10(-8) -2.56 X 10(-7) M/kg) and naloxone (2.75 X 10(-8) -2.2 X 10(-7) M/kg) antagonized the antinociceptive effect of clonidine and morphine, respectively. Higher concentration of yohimbine was required to block the action of morphine. However, naloxone (2.75 X 10(-7) M/kg) did not block the antinociceptive effect of clonidine. In vivo equivalents of pA2 values for morphine-naloxone and clonidine-yohimbine pairs were calculated and found to be 7.09 and 7.45, respectively. The probable involvement of a common antinociceptive site for the observed phenomenon is discussed.

Adrenergic alpha-Agonists↗
PubMed1985

GABAergic, dopaminergic and cholinergic interactions in perphenazine-induced catatonia in rats.

Anticatatonic effects of systemic and intracerebroventricularly administered GABAergic agents (GABA, muscimol piracetam, sod. valproate) were studied in rats against perphenazine-induced catatonia. All GABAergic agents, except piracetam, were found to posses anticatatonic actions as they significantly blocked perphenazine-induced catatonia. When these GABAergic agents were administered simultaneously with anticholinergic (scopolamine) or dopaminergic (bromocriptine) substances there was potentiation of the anticatatonic effect. The protective effect of GABAergic agonists and GABA antagonist and its modification by anticholinergic and dopaminergic agents has been explained on the basis of neurotransmitter interaction.

Animals↗
PubMed1984

P-1 purinoceptor antagonism by clonidine in the rat caecum.

Adenosine as well as 2-chloroadenosine induced concentration-dependent relaxation of the rat caecum. Although clonidine (10(-9)-10(-6)M) did not exhibit any effect per se yet it shifted the concentration-response curve for adenosine as well as 2-chloroadenosine to the right in a parallel fashion without diminishing the maximal response. The pA2 value for the interaction of clonidine with adenosine was found to be 8.71 (slope 0.92). Guanfacine, another alpha 2 agonist, did not modify the adenosine-, 2(2)-chloroadenosine-induced relaxant effects. These observations indicated that clonidine blocks P1- purinoceptors competitively without any involvement of alpha 2-receptors.

Adenosine↗
PubMed1984

Mechanism of potentiation by diazepam of adenosine response.

Diazepam (3 microM) potentiates the adenosine-induced relaxation of caecum. Other benzodiazepine receptor ligands, such as inosine and hypoxanthine, failed to modify adenosine responses. Diazepam failed to further modify the dose-response curve to adenosine obtained in the presence of dipyridamole, and uptake inhibitor. Diazepam and dipyridamole did not affect the responses to 2-chloroadenosine. The relaxant effect of adenosine was not blocked by Ro 15-1788, a benzodiazepine receptor antagonist. These observations indicated that diazepam potentiated adenosine response by inhibiting the uptake of purine nucleotide and, that the benzodiazepine receptor is not purinergic in nature in the rat caecum.

2-Chloroadenosine↗