Effects of amantadine on modification of dopamine dependent behaviours by molindone.

Amantadine, a dopamine agonist is reported to act by releasing dopamine from the dopaminergic nerve terminals as an anti-Parkinsonian drug. In the present behavioural study in the rat, molindone-induced catalepsy and ptosis, which are dopamine dependent-behaviors are reversed by amantadine. Amantadine has also revered molindone-induced inhibition of traction response in mice. Our study indicates that amantadine, like other DA agonists, e.g. amphetamine and apomorphine can antagonize or even reverse the neuroleptic induced dopaminergic behaviors.

Effects of yohimbine on dopamine dependent behaviours in rats and mice.

In the present study we have investigated the effect of yohimbine on dopamine-dependent behaviours in rats and mice. Yohimbine (1.25 to 10 mg/kg, ip) failed to block the conditioned avoidance response in rats, to inhibit the traction response in mice and to induce catalepsy in rats and mice. Pretreatment with yohimbine (1.25 to 10 mg/kg, ip) had no significant effect on apomorphine stereotypy in rats and apomorphine induced cage climbing behaviour in mice. However, pretreatment with yohimbine (1.25 to 10 mg/kg. ip) significantly increased the intensity of methamphetamine stereotypy and antagonised haloperidol catalepsy in rats. Our findings indicate that yohimbine does not possess postsynaptic striatal and mesolimbic D-2 dopamine receptor blocking activity.

Effect of inhibition of lens membrane Na+-K+ ATPase by ouabain pre-treatment--an in vitro study.

The precise factors responsible for the cataract formation are not known. The role of Na+-K+-ATPase in maintaining ionic concentration of lens and lens membrane permeability and its involvement in the formation of cataracts has been of recent interest. Thus the present study was undertaken to study the effect of pre-treatment with Ouabain, a known Na-K-ATPase inhibitor, on the intra-lenticular ionic concentration and the rule of lens membrane permeability in cataractogenesis. Fresh goat lenses were used for the experimental work. Isolated lens culture technique was used. The electrolytes were estimated before and 24 hours after Ouabain pre-treatment. The electrolyte pattern showed significant changes after pre-treatment with Ouabain. Lens sodium ion concentration increased significantly with a concommitant decrease in potassium ion concentration. Intra-lenticular chloride concentration also showed a significant increase as compared to control. Calcium and magnesium ion concentrations also showed slight increase after the inhibition of Na+-K+-ATPase system by Ouabain.

Antagonism of bromocriptine-induced cage climbing behaviour in mice by the selective D-2 dopamine receptor antagonists, metoclopramide and molindone.

Bromocriptine (5-30 mg/kg, ip), 2 hr after administration, induced cage climbing behaviour in mice. Pretreatment with haloperidol, an antagonist of both D-1 and D-2 dopamine receptors, metoclopramide and molindone, the selective D-2 dopamine receptor antagonists, effectively antagonised bromocriptine-induced climbing behaviour. The results indicate that bromocriptine most probably induces climbing behaviour in mice by stimulating the postsynaptic striatal D-2 dopamine receptors.

Correlation between serum choline esterase and serum albumin in leprosy.

The clinical material included 255 cases of leprosy consisting of Tuberculoid leprosy (74), Lepromatous leprosy (116), Lepromatous leprosy with lepra reaction. Liver biopsy could be performed on 50 cases of Lepromatous leprosy. Specific granulomatous changes and parenchymal cell damage were the significant findings. Serum choline esterase and serum albumin are synthesized in liver. Serum Choline esterase levels in the present study decreased abruptly with exacerbation of the disease but the serum albumin levels declined gradually and slowly. Possible hypothesis to explain the correlation and uneven fall in activity is discussed at the cellular level.

L.D.H. isoenzymes sub-unit ratio in leprosy and the effect of clofazimine treatment on L.D.H. isoenzymes sub-unit.

The clinical material for our studies of serum total LDH activity and LDH isoenzymes in leprosy included 255 patients consisting of Tuberculoid (74), Lepromatous leprosy (116), and Lepromatous leprosy with lepra reaction (65). 20 patients with suspected DDS resistance and repeated attacks of lepra reactions were selected for Clofazimine studies. All leprosy patients exhibited higher total LDH activity as compared to normals. M/H ratio was significantly increased in patients of Lepromatous leprosy and correlated closely with the clinical severity and advancement of disease. Tuberculoid leprosy patients showed values close to normals. Hence M/H ratio could demarcate two polar types of leprosy i.e. Tuberculoid and Lepromatous leprosy. Clofazimine treatment over a period of one year in patients with suspected DDS resistance and repeated attacks of lepra reaction decreased total LDH activity and M/H ratio considerably. Fall in M/H ratio during Clofazimine treatment could be attributed to the clearance of 'M' subunits by the drug due to removal of blockade of R.E.S. system produced by lepra bacilli.

Antagonism of apomorphine-induced cage climbing behaviour and methamphetamine stereotypy by fenfluramine in mice.

Pretreatment with fenfluramine (5 and 10 mg/kg, ip) in doses which induced head twitches was found to antagonize apomorphine-induced cage climbing behaviour and methamphetamine stereotypy in mice. Since fenfluramine (5 and 10 mg/kg) did not induce catalepsy it indicates that fenfluramine lacks postsynaptic striatal and mesolimbic dopamine receptor blocking activity and it is possible that the fenfluramine-induced enhancement of central 5-hydroxytryptamine neuronal transmission may be responsible for its antagonistic effect on apomorphine-induced climbing behaviour and methamphetamine stereotypy.

Thalidomide in lepra reaction (ENL) in lepromatous leprosy patients.

Six male bacteriologically highly positive patients of lepromatous leprosy with ENL reaction not adequately controlled by conventional antireaction drugs were put on thalidomide 400 mg per day in four divided doses. Reaction was controlled between 13th to 18th day of therapy. There was no change in the bacteriological status. Liver functions, renal functions and hemogram were normal before therapy and remained unaltered at the end of treatment. Apart from fatigue, drowsiness and occassional constipation, thalidomide had no adverse effect. Control of ENL reaction by thalidomide in these patients is probably due to its immunosuppressive effect, more likely by its stablising action on lysosomes.

Once monthly rifampicin (1200 mg) plus daily dapsone (100 mg) and clofazimine (100 mg) in the initial treatment of lepromatous leprosy.

The therapeutic effect of rifampicin 1200 mg once monthly and 100 mg clofazimine daily for the first six months of treatment was evaluated in 30 patients of bacteriologically positive lepromatous leprosy patients. Moderate to marked clinical improvement was seen in all the patients and a very rapid bacteriological regression as indicated by the decrease in bacteriological and morphological indices of the skin within one week. Seven patients become MI negative at one month and three months and 13 at the end of nine months. Two patients became MI and BI negative at the end of six months and six at the end of nine months. These observations clearly establish the high therapeutic efficacy and practicability of the three drug regimen. Once monthly rifampicin is highly effective and well tolerated, and has many advantages like low cost, better patient compliance and reliability of the treatment. Addition of clofazimine to rifampicin and dapsone prevents the emergence of E.N.L. reactions which were seen during treatment with once monthly rifampicin and daily dapsone. This regimen is thus ideal for initial, intensive treatment of lepromatous leprosy and may help in preventing the spread of the disease and development of dapsone resistance.

Effect of alpha-methyl-p-tyrosine on neuroleptic-induced catalepsy in rat.

Pretreatment with alpha-methyl-p-tyrosine, a tyrosine hydroxylase inhibitor, was found to increase the intensity of catalepsy induced by haloperidol, chlorpromazine and molindone. The drug probably decreases the synthesis of dopamine and makes less dopamine available for release and to compete with the neuroleptic for the postsynaptic striatal dopamine receptor sites with resultant potentiation of the neuroleptic-induced catalepsy.

Effect of drugs influencing central 5-hydroxytryptamine mechanisms on amantadine-induced stereotyped behaviour in the rat.

Pretreatment with L-tryptophan, a precursor of 5-HT, was found to decrease the intensity of stereotyped behaviour induced by amantadine, while methysergide, a 5-HT antagonist, was found to increase the intensity of amantadine-induced stereotypy. These results suggest that the intensity of amantadine-induced stereotypy depends on the balance between central dopamine and 5-HT systems and that the central 5-HT systems may have an opposing, tonic effect upon central dopamine systems involved in the mediation of stereotypy. In contrast to L-tryptophan, however, pretreatment with quipazine, a 5-HT agonist, and clomipramine, a selective 5-HT neuronal reuptake blocker, was found to potentiate the stereotyped behaviour induced by amantadine.

Experimental evaluation of the antidepressant and neuroleptic activity of maprotiline.

Maprotiline, a tetracyclic antidepressant drug, was evaluated for antidepressant and neuroleptic activity. In antidepressant tests, maprotiline antagonized reserpine-induced ptosis in rats but, unlike the tricyclic antidepressants, was found to antagonize methamphetamine stereotypy in rats, to decrease the intensity of L-dopa induced behavioural syndrome in pargyline-pretreated mice and to be ineffective in intensifying the 5-HTP induced behavioural syndrome. In neuroleptic tests, maprotiline was found to, antagonize apomorphine-induced cage climbing behaviour, induce catalepsy, inhibit the CAR and traction response, decrease the spontaneous motor activity and exploratory behaviour, and to potentiate the hypnotic effect of pentobarbitone. Our results indicate that maprotiline exhibits a profile of activity which resembles the neuroleptics and most probably exerts post-synaptic striatal DA receptor blocking activity.