Anti-inflammatory property of ranitidine, a specific H2-receptor antagonist.

The effects of ranitidine (2 mg/kg, po) and phenylbutazone (100 mg/kg po) have been studied in different models of acute and chronic inflammation in rats. Ranitidine showed significant anti-inflammatory activity in the four models used. This observation supports the concept that histamine has a pro-inflammatory role that is mediated via stimulation of H2-receptors.

Effect of bupropion on dopamine and 5-hydroxytryptamine-mediated behaviour in mice.

When bupropion (12.5-50 mg kg-1) was administered 30 min before methamphetamine it significantly antagonized methamphetamine-induced stereotyped behaviour in mice, but when given 5 min after methamphetamine it significantly potentiated the behaviour. When it was administered to mice pretreated with 100 mg kg-1 pargyline, intense locomotor stimulation and stereotyped behaviour was observed whereas when clomipramine was administered similarly the animals showed locomotor stimulation, head twitches and abduction and extension of hind limbs. Unlike clomipramine, bupropion failed to potentiate the 5-hydroxytryptamine-mediated behaviour seen after 5-hydroxytryptophan, 100 mg kg-1, i.v. These observations are in agreement with reports that bupropion is more potent as an inhibitor of dopamine uptake than as an inhibitor of 5-hydroxytryptamine uptake in-vitro.

Effect of one year clofazimine therapy on autonomic functions in lepromatous leprosy with lepra (ENL) reaction.

Twenty patients of either sex of Lepromatous leprosy with frequent type II (ENL) reactions were selected for the study after exclusion of autonomic disorders. ANS functions were evaluated before and after Clofazimine therapy at an interval of two months for one year. Sweat function test, valsalva manoeuvre, Histamine triple response, cold pressor test and Homatropine instillation were carried out in twenty normal healthy volunteers (controls) and the (ENL) patients. Clofazimine was administered initially 100 mg three times daily for one month and then gradually reduced to a dose of 100 mg biweekly for the last three months. Before the clofazimine therapy, eighteen patients had abnormal sweat functions, five patients had abnormal valsalva score, five patients had abnormal cold pressor response and all the eighteen patients had abnormal histamine triple response test. Homatropine instillation test was normal in all the patients. ANS functions did not improve significantly with Clofazimine therapy, except in one patients with abnormal cold pressor response who showed slight improvement in pressor response which, however, did not reach the normal value. ANS function tests indicate complete involvement of local axon reflex and hyporeactivity of sympathetic system and cardiac regulatory mechanisms in these patients. Parasympathetic system seems to be normal as seen from Homatropine instillation test.

Clofazimine in lepra (ENL) reaction, one year clinical trial.

Twenty patients of lepromatous leprosy with lepra reaction and suspected dapsone resistance were treated with tapering doses of clofazimine. Clinical assessment was carried out every week. Bacteriological examination was carried out every six month. Fifteen patients became reaction free at the end of three months and severity and frequency of reactions was reduced in other patients. Nerve tenderness, arthralgia, nodular eruptions and all other signs and symptoms except anaesthesia showed complete recovery in fifteen patients and severity of the reactions was reduced in others. Gynaecomastia regressed in two out of three patients within nine months. In a majority of patients, the BI and MI was reduced at the end of 3 months, and further reduced after 6 months, and in one case both BI and MI became negative. Clinical and bacteriological improvement is attributed to the antibacterial effect of clofazimine while reduction in incidence of (ENL) reactions was attributed to anti-inflammatory effect of clofazimine. Regression of gynaecomastia may be due to either improvement of involvement of testes or liver or both. Apart from dyschromia clofazimine did not produce any severe side effects or toxicity.

Involvement of histaminergic mechanisms in the cataleptogenic effect of morphine in mice.

Intraperitoneally administered morphine induced catalepsy in mice. Morphine pretreatment however, failed to antagonize apomorphine-induced cage climbing behaviour thereby ruling out the possibility of its possessing DA receptor blocking activity. Pretreatment with L-histidine, a precursor of histamine, and atropine, potentiated the cataleptic effect of morphine whilst pretreatment with chlorcyclizine, an H1 receptor blocker, and naloxone, a morphine antagonist, antagonized morphine-catalepsy. Pretreatment with metiamide, an H2 receptor blocker, and methysergide, a 5-HT antagonist, did not significantly alter the cataleptic effect of morphine. The results with L-histidine and chlorcyclizine suggest an involvement of central histaminergic mechanisms in the cataleptogenic effect of morphine in mice. Further, as the cataleptic effect of morphine was also antagonized by naloxone it appears that the interaction of morphine with the central histaminergic mechanisms is mediated through specific opiate receptors.

Effects of baclofen on dopamine-dependent behaviors in mice.

Baclofen, the parachlorophenyl analog of GABA, was found to induce catalepsy and to inhibit the traction response in mice. However, baclofen pretreatment, instead of antagonizing methamphetamine stereotypy and apomorphine-induced cage climbing behavior, was found to potentiate these behaviors, thereby ruling out the possibility of its possessing postsynaptic dopamine (DA) receptor blocking activity. The possible mechanism involved in the induction of catalepsy and in the inhibition of the traction response by baclofen is discussed on the basis that baclofen, by inhibiting the firing of the nigrostriatal and mesolimbic DA neurons, reduces the release of DA and thereby produces a functional lack of DA at postsynaptic DA receptor sites with resultant induction of catalepsy and inhibition of the traction response. Further, the hyper-responsiveness to methamphetamine and apomorphine is explained on the basis that, as the postsynaptic DA receptors are acutely deprived of their transmitter, following baclofen pretreatment, they become supersensitive to the DA agonists.

Effect of L-histidine pretreatment on methamphetamine induced sterotyped behaviour in rats.

Pretreatment with L-histidine precursor of histamine was found to delay the onset, shorten the duration and decrease the intensity of stereotyped behaviour induced by methamphetamine while chlorcylizine a H1 receptor blocker was found not only to potentiate methamphetamine induced sterotyped behaviour but also to block the inhibitory effect of L-histidine on methamphetamine stereotypy. Our results indicate that the central histaminergic system by exerting a modulatory influence on the striatal dopaminergic system may influence the functioning of the extrapyramidal motor system.

Effect of drugs influencing central serotonergic mechanisms on methamphetamine-induced stereotyped behavior in the rat.

Pretreatment with L-tryptophan, a precursor of serotonin, was found to decrease the intensity of stereotyped behavior induced by methamphetamine, while methysergide, a serotonin antagonist, was found to increase the intensity of methamphetamine-induced stereotyped behavior. These results suggest that the intensity of methamphetamine-induced stereotypy depends on the balance between central dopaminergic and serotonergic systems and that the central serotonergic system may have an opposing, tonic effect upon central dopaminergic systems involved in the mediation of stereotypy. In contrast to L-tryptophan, however, pretreatment with quipazine, a serotonin agonist, and clomipramine, a selective, serotonin neuronal uptake blocker, was found to potentiate the stereotyped behavior induced by methamphetamine. The probable mechanisms by which quipazine and clomipramine might have potentiated the methamphetamine-induced stereotypy are discussed.