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Biomedical subjects

A K Mehta

Publications and source records attributed to A K Mehta.

51 records · Page 3Linked to original sources
PubMed1986

Comparison of anticonvulsant effect of pentobarbital and phenobarbital against seizures induced by maximal electroshock and picrotoxin in rats.

Pentobarbital and phenobarbital exhibited anticonvulsant effect against maximal electroshock (MES) and picrotoxin-induced seizures in rats. Bicuculline, a GABAA receptor antagonist, reversed the anticonvulsant effect of pentobarbital, but not of phenobarbital, at a dose having no effect per se. Although picrotoxin (2 mg/kg, IP) potentiated MES seizures, it did not reverse the anticonvulsant effect due to either pentobarbital or phenobarbital. GABAB receptor antagonists such as delta-amino-n-valeric acid and homotaurine failed to modify the anticonvulsant effect due to pentobarbital or phenobarbital. Furthermore, GABAA agonist muscimol but not baclofen, a GABAB receptor agonist, exhibited the anticonvulsant effect against MES-induced seizures. However, baclofen when combined with sub-effective dose of pentobarbital or phenobarbital offered protection against MES seizures. Pentobarbital and phenobarbital were effective in almost equivalent doses against MES, as well as against picrotoxin-induced seizures. These observations indicated that pentobarbital exhibits anticonvulsant effect against MES seizures through the involvement of GABAA receptors, and activation of GABAB receptors alone does not seem to play any significant role in MES seizures and in the anticonvulsant effect of pentobarbital. However, activation of GABAB receptor does potentiate the facilitatory effect of barbiturates on GABAAergic transmission and in their anti-MES effect. Moreover, these results also suggest that the anticonvulsant effect of barbiturates against MES-seizures may involve other mechanisms in addition to GABAAergic transmission.

Amino Acids↗
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

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↗
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↗
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↗
PubMed1983

Possible mechanism of digoxin-induced convulsions.

Intraventricular (IVT) administration of digoxin (7.5 micrograms) induced 'popcorn-type' convulsions in rats. Though the convulsions looked similar to morphine-induced seizures, naloxone failed to antagonize these effects. Other anticonvulsants like phenobarbitone, ethosuximide, or GABAergic substances like piracetam and semicarbazide also had no protective effect against digoxin-induced convulsions. While calcium chloride potentiated these effects of digoxin, phenytoin, magnesium chloride, and potassium chloride treatment showed blocking actions. These observations suggest the involvement of Na/K-ATPase system in digoxin-induced convulsions. Clonidine and diazepam also provided protection against digoxin-induced convulsions through an unknown mechanism.

Animals↗
PubMed1983

Effect of purinergic substances on rectal temperature in mice: involvement of P1-purinoceptors.

Effect of adenosine, 2-chloroadenosine (P1-purinoceptor agonists) and adenosine triphosphate (ATP), adenosine-5'-tetraphosphate (P2-purinoceptor agonists) on body temperature was studied in mice. Adenosine (7.5-200 mg/kg) as well as 2-chloroadenosine (0.25-7.5 mg/kg) induced hypothermia in a dose-dependent manner. However, ATP or adenosine-5'-tetraphosphate did not show any effect on body temperature. Caffeine and theophylline, P1-purinoceptor antagonists, blocked the hypothermic response of adenosine and 2-chloroadenosine. Treatment with quinidine or phenoxybenzamine (non-specific P2-purinoceptor antagonists) did not modify the hypothermic response. Similarly, treatment with drugs which modify adrenergic (reserpine, propranolol, labetalol or haloperidol), serotonergic (cyproheptadine) or histaminergic functions failed to block adenosine or 2-chloroadenosine-induced hypothermia. These results demonstrated that P1-purinoceptors mediated the hypothermic response of these purines.

2-Chloroadenosine↗
PubMed1983

Evidence for the presence of P1- and P2-purinoceptors in rat caecum.

Adenosine, 2-chloroadenosine, adenosine triphosphate (ATP) and adenosine tetraphosphate induced concentration-dependent relaxation of rat caecum. Caffeine as well as theophylline, at concentrations (25-100 microM) lower than that known to produce significant phosphodiesterase inhibition, shifted the concentration-response curve for adenosine to the right in a parallel fashion without diminishing the maximal response. The pA2 values for caffeine and theophylline against adenosine were found to be 4.6 +/- 0.26 (slope = 0.97 +/- 0.05) and 4.9 +/- 0.28 (slope = 0.98 +/- 0.07), respectively. Though the relaxant effect of adenosine tetraphosphate was blocked in a non-competitive manner by quinidine (5 microM) and phenoxybenzamine (25 microM), theophylline or caffeine (50 microM) failed to block this response. Similarly, quinidine also blocked the relaxant effect of ATP in a non-competitive manner. Besides, the relaxant effect due to adensine was rapid in onset as compared to a slow relaxant effect of ATP. These observations suggest the presence of P1- and P2-purinoceptors in the caecum. The activation of these receptors by adenosine and ATP, respectively, leads to relaxation of the tissue.

2-Chloroadenosine↗
PubMedDate not supplied

Effect of various pharmacological agonists on the rat caecum-appendix preparation: a preliminary study.

A preliminary study with various pharmacological agents revealed the presence of contractile muscarinic and H1-histamine receptors as well as inhibitory alpha- and beta-adrenoceptors and purinoceptors in rat caecum-appendix. Histamine also produced indirect actions mediated through the release of catecholamines. 5-Hydroxytryptamine produced variable response, the contractile response was mediated through 5-HT receptors and the relaxant response through the release of catecholamines.

Acetylcholine↗