Antidiarrhoeal activity of Geranium incanum Burm. f. (Geraniaceae) leaf aqueous extract in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Geranium incanum Burm. f. (Geraniaceae) is used in South Africa especially in rural communities by traditional medicine practitioners to treat diarrhoea. However, scientific evidence does not exist in any literature to corroborate the claim of therapeutic success of the plant species in diarrhoea. AIM OF STUDY: The study intended to investigate the antidiarrhoeal activity of the leaf aqueous extract of Geranium incanum in mice. MATERIALS AND METHODS: Castor oil induced diarrhoeal test was used to assess the antidiarrhoeal activity of Geranium incanum. Gastrointestinal tract transit of charcoal meal test was used to assess the antipropulsive activity of the plant extract while the acute toxicity study and phytochemical analysis were carried out using well established protocols and methods. RESULTS: The antidiarrhoeal activity of Geranium incanum was investigated by studying the effect of leaf aqueous extract of the plant species on castor oil-induced diarrhoea in mice. The leaf aqueous extract of Geranium incanum significantly reduced faecal output in castor oil -induced diarrhoea and also significantly reduced the number of diarrhoeal episodes. Geranium incanum significantly delayed the onset of diarrhoea induced by castor oil and significantly reduced the number of animals exhibiting diarrhoea. Loperamide, a standard antidiarrhoeal drug, produced similar effects to the leaf aqueous extract of Geranium incanum on castor oil-induced diarrhoea. Both Geranium incanum and loperamide significantly reduced the intestinal propulsion of charcoal meal in mice. The phytochemical analysis of the leaves revealed the presence of tannins, saponins particularly steroidal saponin, and flavonoids. The LD(50) of the plant species obtained was greater than 4000 mg/kg (p.o.). CONCLUSION: The data obtained indicate that the leaf aqueous extract of Geranium incanum has both antidiarrhoeal and antipropulsive activities The data also show that the plant material given orally may be safe and/or non toxic in mice. However, further investigation on the acute toxicity and on the mechanism of the antidiarrhoeal effect of the plant species needs to be carried out.

Antipyretic and antinociceptive properties of Mentha longifolia Huds. (Lamiaceae) leaf aqueous extract in rats and mice.

The antipyretic and antinociceptive properties of Mentha longifolia Huds. (Lamiaceae) leaf aqueous extract were investigated using lipopolysaccharide (LPS)-induced pyrexia in rats, and acetic acid and hot plate analgesia tests in mice. Pentoxifylline, paracetamol and morphine were used as standard drugs for comparison. M. longifolia leaf aqueous extract and pentoxifylline (37.5-150 mg/kg i.p.) significantly (P < 0.05-0.02) reduced the LPS (50 g/kg i.m.)-elicited pyrexia. Pentoxifylline (50 mg/kg i.p.) also significantly (P < 0.01) reduced LPS (50 g/kg i.m.)-induced pyrexia. M. longifolia leaf aqueous extract (6.25-100 mg/kg i.p.) and paracetamol (500 mg/kg i.p.) profoundly inhibited the writhes produced by 3% acetic acid. Furthermore, the plant extract (25-400 mg/kg i.p.) and morphine (10 mg/kg i.p.) significantly (P < 0.001) delayed the hot plate reaction time in mice. The LD(50) values for oral and intraperitoneal administration of the plant extract were > 3200 mg/kg and 1730 mg/kg, respectively. Phytochemical analysis revealed the presence of flavonoids, saponins, tannins, reducing sugars, cardiac glycosides and triterpene steroids in the leaves of M. longifolia. These data indicate that M. longifolia leaf aqueous extract has antipyretic and antinociceptive properties. Furthermore, the relatively high LD(50) values obtained for oral and intraperitoneal administration of the plant extract demonstrate that the plant extract is non-toxic to mice.

Anticonvulsant activity of Cotyledon orbiculata L. (Crassulaceae) leaf extract in mice.

The anticonvulsant activity of Cotyledon orbiculata L. (Crassulaceae) was investigated by studying the effects of both aqueous and methanol extracts of the plant species on seizures induced by pentylenetetrazole, bicuculline, picrotoxin and N-methyl-dl-aspartic in mice. Aqueous extract of Cotyledon orbiculata (50-400mg/kg, i.p.) and methanol extract (100-400mg/kg, i.p.) significantly prolonged the onset of tonic seizures induced by pentylenetetrazole (95mg/kg, i.p.). Methanol extract (400mg/kg, i.p.) also significantly reduced the incidence of the seizures. One hundred to two hundred milligrams/kilogram (i.p.) of aqueous extract of Cotyledon orbiculata significantly delayed the onset of the tonic seizures induced by bicuculline (40mg/kg, i.p.), picrotoxin (12mg/kg, i.p.) and N-methyl-dl-aspartic acid (NMDLA, 400mg/kg, i.p.). Similarly, methanol extract (100-400mg/kg, i.p.) significantly delayed the onset of the tonic seizures induced by bicuculline (40mg/kg, i.p.) and picrotoxin (12mg/kg, i.p.) while 100mg/kg (i.p.) significantly delayed the onset of N-methyl-dl-aspartic acid (NMDLA, 400mg/kg, i.p.)-induced seizures. Methanol extract (200mg/kg, i.p.) significantly reduced the incidence of the seizures induced by bicuculline (40mg/kg, i.p.). Phenobarbitone (12mg/kg, i.p.) and diazepam (0.5mg/kg, i.p.) effectively antagonized only seizures induced by PTZ (95mg/kg, i.p.), bicuculline (40mg/kg, i.p.) and picrotoxin (12mg/kg, i.p.). Phenytoin (30mg/kg, i.p.) did not affect any of the seizures to any significant extent. The data obtained suggest that both aqueous and methanol extracts of Cotyledon orbiculata have anticonvulsant property and may probably be affecting both gabaergic and glutaminergic mechanisms to exert its effect. The phytochemical analysis carried out revealed the presence of cardiac glycosides, saponins, tannins, reducing sugar and triterpene steroids in the plant extract.

An assessment of two Carpobrotus species extracts as potential antimicrobial agents.

For centuries, indigenous people in South Africa have used a variety of medicinal herbs to treat chronic infections. This investigation focused on two Carpobrotus species belonging to the family, Aizoaceae, in an attempt to assess their antimicrobial potential. Extracts of varying polarities of the plants were prepared and tested against Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans and Mycobacterium smegmatis. For the disc diffusion method, Ciprofloxacin (40 microg/disc) served as positive control for S. aureus, P. aeruginosa and M. smegmatis, whereas amphotericin B (25 microg/disc) was the control for C. albicans. A sample concentration of 10 mg/ml was used. Minimum inhibitory concentrations (MIC) were determined by two-fold serial dilution. Phytochemical analysis was completed to test for the presence of flavonoids, hydrolysable tannins, phytosterols and aromatic acids. The ethyl acetate extracts (21 microl of 95 mg/ml) were used for bio-autography, together with TLC analyses. Carpobrotus muirii and Carpobrotus quadrifidus showed antimicrobial activity against S. aureus and M. smegmatis in the disc diffusion method and inhibition against S. aureus and M. smegmatis was observed by clear zones on the TLC plate. This investigation confirms that extracts of these Carpobrotus species that are used as indigenous medicines, exhibit anti-bacterial activity. This scientific information can serve as an important platform for the development of inexpensive, safe and effective natural anti-infective medicines.

Anticonvulsant activity of aqueous extract of Leonotis leonurus.

Water extract of Leonotis leonurus was tested for anticonvulsant activity against seizures produced in mice by pentylenetetrazole, picrotoxin, bicuculline and N-methyl-DL-aspartic acid (intraperitoneal injections). L. leonurus extract in the doses of 200 and 400 mg/kg respectively protected 37.5% and 50% of animals used and significantly (p < 0.05; Student's t-test) delayed pentylenetetrazole (90 mg/kg)-induced tonic seizures. Similarly, the same doses of L. leonurus extract significantly (p < 0.05; Student's t-test) delayed the onset of tonic seizures produced by picrotoxin (8 mg/kg) and N-methyl-DL-aspartic acid (400 mg/kg). However, all the doses of aqueous extract of L leonurus used did not alter the seizures induced by bicuculline (20 mg/kg) to any significant extent. The data suggest that the extract of L. leonurus has anticonvulsant activity and may probably be acting through non-specific mechanisms, since it affects both gabaergic and glutaminergic systems. High performance liquid chromatography (HPLC) and phytochemical tests carried out respectively show a spectrum profile, characteristic of L. leonurus and the presence of alkaloids, saponins and tannins in the extract.

Analgesic and antipyretic effects of Dodonaea angustifolia and Salvia africana-lutea.

Water extracts of Dodonaea angustifolia L. and Salvia africana-lutea L., were investigated for analgesic and antipyretic activities using acetic acid writhing and hot plate tests, and lipopolysaccharide (LP)-induced pyrexia test in mice and rats, respectively. D. angustifolia and S. africana-lutea significantly inhibited acetic acid-induced writhing and also significantly delayed the time of reaction of mice to thermal stimulation produced by the hot plate. D. angustifolia and S. africana-lutea significantly reduced fever induced by LP. Paracetamol produced similar effects to D. angustifolia and S. africana-lutea on the acetic acid-induced writhing but has no effect on hot plate-induced nociception and on pyrexia produced by LP. These data indicate the analgesic and antipyretic potential of D. angustifolia and S. africana-lutea.

Effects of Tarchonanthus camphoratus and Eriocephalus africanus on nociception in mice and pyrexia in rats.

The affects of water extracts of the leaves of T. camphoratus and E. africanus on acetic acid- and hotplate-induced nociception and lipopolysaccharide-induced pyrexia were investigated. The writhing induced by acetic acid was significantly attenuated by T. camphoratus (50-100 mg/kg, i.p.), and E. africanus (50-200 mg/kg, i.p.). Similarly, the pain produced by the hot-plate was significantly antagonized by T. camphoratus (100 mg/kg, i.p.), and E. africanus (50-100 mg/kg, i.p.). T. camphoratus (100 mg/kg, i.p.), and E. africanus (100-200 mg/kg, i.p.) significantly attenuated the fever produced by the bacterial endotoxin (lipopolysaccharide, 50 microg/kg, i.m.). Paracetamol (500 mg/kg, i.p.), produced similar effect to T. camphoratus and E. africanus on acetic acid-induced writhes but did not affect the pain and the fever produced by the hot-plate and lipopolysaccharide respectively, to any significant extent. These results indicate that both T. camphoratus and E. africanus have analgesic and antipyretic properties.

Gamma-aminobutyric acid and glutamic acid receptors may mediate theophylline-induced seizures in mice.

The effects of drugs affecting GABA and glutamic acid receptors on theophylline-induced seizures were investigated in mice. Theophylline elicited tonic seizures in mice in a dose dependent manner. Muscimol, DABA and AOAA significantly prolonged the onset and significantly decreased the incidence of theophylline-induced seizures. Baclofen significantly delayed the onset of the tonic seizures induced by theophylline. Bicuculline and picrotoxin significantly shortened the onset and significantly increased the incidence of seizures induced by a low dose of theophylline and also significantly antagonized muscimol-attenuating effect against theophylline seizures. N-methyl-DL-aspartic acid significantly shortened the onset and significantly increased the incidence of seizures elicited by a low dose of theophylline. D-(-)-2-amino-phosphonopentanoic acid effectively delayed the onset and significantly decreased the incidence of seizures elicited by theophylline and also significantly antagonized the potentiating effect of N-methyl-DL-aspartic acid on seizures induced by a low dose of theophylline. Dextromethorphan and ketamine profoundly shortened the onset of theophylline-induced seizures. Clonidine effectively prolonged the onset and significantly decreased the incidence of theophylline-induced seizures. These data indicate that GABA(A) and N-methyl-D-aspartic acid receptors may mediate theophylline-elicited tonic seizures in mice.

Antimicrobial and anticonvulsant activities of Viscum capense.

Dichloromethane, methanol and water extracts of Viscum sapense L.f., of the Loranthaceae family, were tested for antimicrobial activities against Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans. Methanol extract was also tested for activity against seizures in albino mice induced by pentylenetetrazole (PTZ), bicuculline and N-methyl-DL-aspartic acid (NMDLA). Methanol extract of V. capense inhibited the growth of S. aureus. Methanol extract also protected the mice against PTZ- and bicuculline-induced tonic seizures but did not significantly alter NMDLA-induced tonic seizures. The data indicate that the extract of V. capense has antibacterial activity against S. aureus and also anticonvulsant activity.

Propranolol-induced seizures in mice: the role of noradrenaline.

The effects of some noradrenergic agents, phenobarbitone, diazepam and phenytoin on seizures produced by propranolol were investigated in mice. Isoprenaline and DL-threo-3,4-dihydroxyphenylserine (DOPS) effectively antagonized the seizures elicited by propranolol. Pargyline and imipramine significantly attenuated propranolol-induced seizures and also significantly potentiated the protecting effect of DOPS against the seizures. alpha-Methyl-p-tyrosine, disulfiram and reserpine significantly potentiated propranolol-elicited seizures. However, DOPS significantly antagonized the seizure-potentiating effects of alpha-methyl-p-tyrosine, disulfiram and reserpine. Phenylephrine, clonidine, prazosin, idazoxan, phenobarbitone, diazepam and phenytoin did not significantly alter propranolol-induced seizures. These results suggest that propranolol-induced seizures in mice may involve a noradrenergic mechanism mediated via central beta-adrenoceptors.

GABAergic and dopaminergic systems may be involved in seizures induced by pyrimethamine in mice.

1. The effects of some GABAergic and dopaminergic agents on pyrimethamine-induced tonic seizures were investigated in mice. 2. Pyrimethamine dose dependently induced seizures in mice. 3. Muscimol, AOAA and DABA significantly protected mice against pyrimethamine-induced seizures. 4. Bicuculline and picrotoxin effectively potentiated seizures elicited by pyrimethamine and significantly antagonized the protective effect of muscimol against the seizures. 5. Diazepam and phenobarbitone effectively protected mice against seizures elicited by pyrimethamine. 6. L-Dopa significantly potentiated pyrimethamine-induced seizures. 7. Apomorphine and pargyline significantly reduced the latency of seizures induced by pyrimethamine. 8. Haloperidol and pimozide effectively protected mice against pyrimethamine-elicited seizures and also significantly antagonized the potentiating effects of apomorphine and L-dopa on the seizures. 9. Disulfiram significantly potentiated seizures induced by pyrimethamine and also significantly enhanced the seizure-potentiating effect of L-dopa. 10. alpha-Methyl-p-tyrosine effectively protected against seizures induced by pyrimethamine. However, L-dopa significantly potentiated the seizures in alpha-methyl-p-tyrosine-pretreated animals. 11. Muscimol significantly attenuated the potentiating effect of L-dopa on pyrimethamine-induced seizures while bicuculline significantly enhanced the effect of L-dopa. Furthermore, haloperidol significantly potentiated the protective effect of muscimol against pyrimethamine-induced seizures. 12. These results suggest that both GABA and dopamine might be involved in the mechanism(s) of pyrimethamine seizures in mice.

Strychnine-induced seizures in mice: the role of noradrenaline.

1. The effects of some noradrenergic agents on seizures induced by strychnine were investigated in mice. 2. Strychnine (0.5-4 mg/kg, i.p.) dose-dependently produced tonic seizures. 3. DOPS (4-8 mg/kg, i.p.) significantly shortened the latency of seizures elicited by strychnine (2 mg/kg, i.p.). Similarly, DOPS (4 mg/kg, i.p.) effectively increased the incidence and significantly shortened the latency of seizures induced by strychnine (1 mg/kg, i.p.). 4. Imipramine (20-40 mg/kg, i.p.) and pargyline (200 mg/kg, i.p.) significantly shortened the latency of strychnine (2 mg/kg, i.p.)-induced seizures. 5. Phentolamine (5-20 mg/kg, i.p.) effectively antagonised the seizures elicited by strychnine (2 mg/kg, i.p.). Furthermore, phentolamine (10 mg/kg, i.p.) attenuated the seizure-potentiating effect of DOPS (4 mg/kg, i.p.). 6. Propranolol (0.5-2 mg/kg, i.p.) and prazosin (1-2 mg/kg, i.p.) reduced the incidence and significantly delayed the latency of seizures induced by strychnine (2 mg/kg, i.p.). 7. Reserpine (5-10 mg/kg, i.p.) significantly prolonged the latency of strychnine (2 mg/kg, i.p.)-induced seizures. 8. Clonidine (0.25-1 mg/kg, i.p.) dose-dependently and significantly antagonised strychnine (2 mg/kg, i.p.)-induced seizures. 9. Idazoxan (1-4 mg/kg, i.p.) in a dose related manner significantly shortened the latency of seizures induced by strychnine (2 mg/kg, i.p.). Similarly, idazoxan (2 mg/kg, i.p.) profoundly potentiated seizures elicited by strychnine (1 mg/kg, i.p.). Idazoxan (4 mg/kg, i.p.) significantly antagonised the protective effect of clonidine (1 mg/kg, i.p.) against strychnine (2 mg/kg, i.p.)-induced seizures. 10. Disulfiram (3 x 25 - 3 x 100 mg/kg, i.p.) significantly attenuated strychnine (2 mg/kg, i.p.)-induced seizures. DOPS (4 mg/kg, i.p.) significantly potentiated strychnine seizures in disulfiram (3 x 100 mg/kg, i.p.)-pretreated animals. 11. These results indicate that enhancement of noradrenergic neurotransmission potentiates strychnine seizures in mice.

gamma Aminobutyric acid mediation of the anticonvulsant effect of clonidine on pentylenetetrazol-induced seizures in mice.

The effects of muscimol, amino-oxyacetic acid (AOAA), diamino-N-butyric acid (DABA), bicuculline, picrotoxin, diazepam and phenobarbitone on the protective effect of clonidine against pentylenetetrazol-induced seizures were studied in mice. Muscimol, AOAA, DABA, phenobarbitone and diazepam significantly protected mice against pentylenetetrazol-induced seizures and also significantly potentiated the protective effect of clonidine against the seizures. Bicuculline and picrotoxin significantly potentiated seizures induced by pentylenetetrazol and significantly attenuated both the protective effects of muscimol and clonidine against the seizures. These data suggest that activation of gamma-aminobutyric acid systems may underlie the protective effect of clonidine against seizures induced by pentylenetetrazol in mice.

Some behavioural effects of chloroquine in rats suggesting dopaminergic activation.

The effect of chloroquine on open-field behaviour, apomorphine induced stereotypies and haloperidol and pimozide-induced catalepsy was studied in rats. Chloroquine (2.5-10 mg/kg, ip) significantly increased the locomotion frequently of rats in the open-field and also markedly enhanced apomorphine (0.4 mg/kg, sc)-induced locomotion. Haloperidol (0.25 mg/kg, ip) antagonised the increased locomotion frequency produced by chloroquine (5 mg/kg, ip), apomorphine (0.4 mg/kg, sc) and chloroquine plus apomorphine. L-Dopa (50 mg/kg, sc) and benserazide (12.5 mg/kg, ip) plus L-Dopa (50 mg/kg,sc) significantly increased chloroquine (5 mg/kg, ip)-induced locomotion. SCH 23390 (0.2 mg/kg, sc) and sulpiride (30 mg/kg, ip), on the other hand, attenuated chloroquine (5 mg/kg, ip)-induced locomotion. Chloroquine (2.5-5 mg/kg, ip) elicited stereotyped behaviour in rats and significantly potentiated apomorphine (2 mg/kg, sc)-induced stereotypies. Haloperidol (0.25 mg/kg, ip) markedly reduced the stereotypies produced by both chloroquine (5 mg/kg, ip) and apomorphine (2 mg/kg, sc). Both chloroquine (2.5-10 mg/kg, ip) and apomorphine (0.4 mg/kg, sc) significantly delayed the onset and decreased the intensity of catalepsy induced by haloperidol (0.25mg/kg, ip) and pimozide (2mg/kg, ip) respectively. These findings indicate that chloroquine, in low doses, produces excitatory effects and that dopaminergic mechanisms may be involved in the observed effects of chloroquine.

Cimetidine-induced seizures in mice. Antagonism by some GABAergic agents.

The effects of muscimol, aminooxyacetic acid (AOAA), diamino-n-butyric acid (DABA), baclofen, bicuculline, picrotoxin, strychnine, diazepam, phenobarbitone and phenytoin on cimetidine-induced seizures were studied in mice. Cimetidine (400-1000 mg/kg, i.p.) induced dose-dependent tonic convulsion. Muscimol, AOAA and DABA effectively protected mice against cimetidine-induced seizures. Bicuculline and picrotoxin significantly potentiated the seizures induced by cimetidine and effectively antagonized the protective effects of muscimol, AOAA and DABA against the seizures. Diazepam and phenobarbitone significantly protected the mice against cimetidine-induced seizures while phenytoin and strychnine did not significantly alter the seizures. These results indicate that the attenuation of central gamma-aminobutyric acid neurotransmission may underlie cimetidine-induced seizures in mice.

The involvement of noradrenaline, 5-hydroxytryptamine and acetylcholine in imipramine-induced seizures in mice.

The influence of some noradrenergic, 5-hydroxytryptaminergic and cholinergic agents on imipramine-induced seizures were investigated in mice. DL-threo-3,4-dihydroxyphenylserine (DOPS) and pargyline significantly potentiated imipramine-induced seizures. Phentolamine and prazosin significantly attenuated seizures elicited by imipramine and significantly attenuated the seizure-enhancing effect of DOPs. alpha-Methyl-p-tyrosine and reserpine significantly attenuated seizures induced by imipramine. Disulfiram significantly protected mice against imipramine-induced seizures. However, DOPS significantly potentiated seizures induced by imipramine in disulfiram-pretreated animals. Clonidine effectively protected mice against imipramine-induced seizures. Idazoxan, on the other hand, significantly potentiated seizures induced by imipramine and significantly antagonised the protective effect of clonidine against the seizures. 5-HTP, PCPA, cyproheptadine, mianserin, ketanserin and trazodone did not affect imipramine-induced seizures to any significant extent. Physostigmine antagonised seizures induced by imipramine while atropine significantly potentiated the seizures, and significantly attenuated the protective effect of physostigmine against the seizures. These data suggest that enhancement and attenuation of central noradrenergic and cholinergic neurotransmissions respectively, and not 5-HT mechanisms, may underlie imipramine-induced seizures in mice.

Chloroquine-induced seizures in mice: the role of monoaminergic mechanisms.

The influence of some dopaminergic and noradrenergic agents on seizures induced by chloroquine (45-100 mg/kg, i.p.) was investigated in mice. Apomorphine (0.2-0.8 mg/kg, s.c.). L-dopa (25-50 mg/kg, s.c.) benserazide (5 mg/kg, i.p.) plus L-dopa (50 mg/kg, s.c.), pargyline (100 mg/kg, i.p.), FLA-63 (10-20 mg/kg, s.c.) and FLA-63 (10 mg/kg, s.c.) plus L-dopa (50 mg/kg, s.c.) profoundly shortened the latency of seizures induced by chloroquine (65 mg/kg, i.p.). L-Dopa (50 mg/kg, s.c.) weakly reduced the latency and weakly increased the incidence of chloroquine (50 mg/kg, i.p.)-induced seizures. alpha-Methyl-p-tyrosine (25-100 mg/kg, i.p.) dose-dependently and significantly reduced the incidence and significantly prolonged the latency of chloroquine (65 mg/kg, i.p.)-induced seizures. However, L-dopa (50 mg/kg, s.c.) effectively increased the proportion of animals convulsing and effectively reduced the latency of seizures induced by chloroquine (65 mg/kg, i.p.) in alpha-methyl-p-tyrosine-pretreated mice. Haloperidol (0.25-1.0 mg/kg, i.p.) and pimozide (2-4 mg/kg, i.p.) markedly reduced the incidence and markedly prolonged the latency of seizures induced by chloroquine (65 mg/kg, i.p.) in a dose-related manner. However, apomorphine (0.4-0.8 mg/kg, s.c.) and L-dopa (25-50 mg/kg, s.c.) profoundly attenuated the protective effects of haloperidol (0.5 mg/kg, i.p.) and pimozide (4 mg/kg, i.p.) against chloroquine (65 mg/kg, i.p.)-induced seizures.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetic interaction of single doses of quinine and carbamazepine, phenobarbitone and phenytoin in healthy volunteers.

Effects of single doses of quinine on plasma and urine concentrations of carbamazepine, phenobarbitone and phenytoin were studied in healthy volunteers. Quinine (600mg, p.o.) markedly augmented the peak plasma concentrations and area under the curve (AUC [0-24]) values of carbamazepine (200mg,p.o.) and phenobarbitone (120mg,p.o.) but did not affect those of phenytoin (200mg,p.o.). Mean urinary recoveries of carbamazepine, phenobarbitone and phenytoin over 24 hours also profoundly increased with concomitant administration of quinine. These results indicate possible interaction between quinine and carbamazepine or phenobarbitone.

Effects of some GABAergic agents on quinine-induced seizures in mice.

The effects of some GABAergic agents on seizures induced by quinine were studied in mice. Muscimol, AOAA, DABA and baclofen significantly protected mice against quinine-induced convulsions. Bicuculline effectively enhanced quinine-induced convulsions, and significantly attenuated the protective effects of muscimol, AOAA and DABA against convulsions induced by quinine. Diazepam and phenobarbitone significantly protected mice against convulsions induced by quinine. However, phenytoin did not affect quinine-induced seizures to any significant degree. These results indicate that the convulsant effect of quinine may be due to a disturbance in the status of the GABAergic system.

Influence of some dopaminergic agents on antinociception produced by quinine in mice.

1. The analgesic effect of quinine and the influence of some dopaminergic agents on it were studied in mice. 2. Quinine (25-130mg/kg, ip) effectively elicited antinociceptive effect in a dose related manner. 3. D-Amphetamine (2.5-4mg/kg, ip), L-dopa (25mg/kg, sc), L-dopa (25mg/kg, sc) plus benserazide (12.5mg/kg, sc), alpha-methyl-p-tyrosine (50mg/kg, ip) plus L-dopa (25mg/kg, sc) and pargyline (50mg/kg, ip) significantly attenuated the antinociceptive effect of quinine (50mg/kg, ip), while DOPS (4mg/kg, ip) did not affect quinine antinociception. 4. Pimozide (4mg/kg, ip), L-sulpiride (40mg/kg, ip), SCH 23390 (0.2mg/kg, sc) and alpha-methyl-p-tyrosine (50mg/kg, ip) effectively potentiated the antinociceptive effects of quinine (50mg/kg, ip). 5. Pimozide (4mg/kg, ip) also antagonised the antagonistic effect of d-amphetamine (4mg/kg, ip) on the antinociceptive effect of quinine (50mg/kg, ip). 6. These data indicate that quinine elicited antinociception dose dependently. Furthermore, the influence of pimozide, L-sulpiride and SCH 23390 on quinine antinociception suggests the involvement of dopaminergic mechanisms.