Selective D2 Dopamine Agonists Research Articles

Combined effects of modafinil and d-amphetamine in male Sprague–Dawley rats trained to discriminate d-amphetamine

Modafinil is a novel wake-promoting drug with FDA approval for the treatment of sleep-related disorders that has recently been investigated as a potential agonist replacement therapy for psychostimulant dependence. Previous research in animals and humans indicates modafinil has a lower abuse liability than traditional psychostimulants, although few studies have carefully assessed modafinil's stimulus properties in combination with other psychostimulants. The current study trained male Sprague–Dawley rats to discriminate subcutaneous injections of 0.3mg/kg (n=8) or 1.0mg/kg d-amphetamine (n=8) from saline under an FR 20 schedule of food reinforcement and substitution tests were administered with d-amphetamine (0.03–1.0mg/kg, s.c.), modafinil (32–256mg/kg, i.g.), and a low modafinil dose (32mg/kg, i.g.) in combination with d-amphetamine (0.03–1.0mg/kg, s.c.) to determine if these drugs have additive effects. The selective D2 dopamine agonist, PNU-91356A, was also tested as a positive control and ethanol and morphine were tested as negative controls. Results indicate that modafinil produced dose-dependent and statistically significant d-amphetamine-lever responding in both groups and nearly complete substitution in animals trained to discriminate 1.0mg/kg d-amphetamine. Modafinil pretreatment slightly increased the discrimination of low d-amphetamine doses in animals trained to discriminate 0.3mg/kg d-amphetamine. These results support previous findings that modafinil and d-amphetamine may have additive effects. In consideration of recent interests in modafinil as an agonist treatment for psychostimulant dependence, additional preclinical investigations utilizing other methodologies to examine modafinil in combination with other stimulants, such as behavioral sensitization paradigms or drug self-administration, may be of interest.

Die Verbesserung motorischer und nicht-motorischer Symptome bei Parkinson-Patienten unter einer Therapie mit Ropinirol

Ropinirole is a non-ergoline selective D2 dopamine agonist. Its efficacy and safety has been established in several controlled double-blind studies in patients with early and advanced Parkinson's disease. It is assumed that the improvement in the activities of daily living under ropinirole is not only due to the improved motor symptoms but also due to the improvement of non-motor symptoms like symptoms of mood and anxiety. The objective of this post marketing surveillance study was to show that under the conditions of the daily routine in the neurologic practice ropinirole may not only improve motor symptoms, the activity of daily living and complications of the treatment (dystonia, dyskinesia) but also alleviate symptoms of depression and anxiety. A total of 110 neurological practices enrolled 327 patients in early and advanced stages of the disease (139 females, 188-males; mean age: 67 years). They were treated with ropinirole as monotherapy and as adjunctive therapy with l-dopa over a period of 12 - 14 weeks. Selected symptoms of the Unified Parkinson's Disease Rating Scale (UPDRS) part II-IV and symptoms of depression and anxiety were rated by the clinicians. Mood and functional impairment in job, family and social life were rated by the patients using selected items of the Beck Depression Inventory and the Sheehan Disability Scale (SDS). The different subtypes, i. e. the akinetic-rigid, tremor-dominant and the mixed subtype, are described separately. The total UPDRS score at baseline was similar for all three subtypes and there was also a similar improvement in the three groups under ropinirole. Both according to self-rating and to clinician rating the symptoms of depression and anxiety at baseline were more severe in the akinetic-rigid and the mixed subtype compared to the tremor-dominant subtype. The symptoms considerably improved and were reduced by 48 % under therapy with ropinirole. Adverse events were reported by 7.7 % of the patients. The surveillance study has shown that ropinirole may improve not only motor symptoms, activities of daily living and complications of treatment but also symptoms of mood and anxiety.

CASSIA SIAMEA INDUCED HEPATITIS, A CASE REPORT OF PHYTOMEDICINE SIDE EFFECT

CASSIA SIAMEA INDUCED HEPATITIS, A CASE REPORT OF PHYTOMEDICINE SIDE EFFECT

Attenuation of the locomotor-sensitizing effects of the D2 dopamine agonist bromocriptine by either the D1 antagonist SCH 23390 or the D2 antagonist raclopride.

Injections of the selective D2 dopamine agonist bromocriptine (5.0 mg/kg, IP) produced progressively stronger locomotion over 10 days of repeated testing. Concurrent treatment with either the D1 antagonist SCH 23390 (0.01 or 0.1 mg/kg, IP) or the D2 antagonist raclopride (0.1 or 1.0 mg/kg, IP) suppressed bromocriptine-induced locomotion on treatment days and attenuated or blocked the progressive increases in locomotion that accompanied repeated injections of bromocriptine alone. The fact that D1 and D2 antagonists each block the acute actions of bromocriptine and attenuate the development of bromocriptine sensitization is suggested to imply a striatal rather than a ventral tegmental mechanism for the sensitization produced by repeated treatments with direct dopamine agonists.

In vivo effects of serotonergic agents on alpha-melanocyte-stimulating hormone secretion.

We used an in vivo pharmacological approach to investigate the potential influence of serotonin (5-HT) on peptide release from the intermediate lobe (IL) of the rat pituitary. Plasma levels of alpha-melanocyte-stimulating hormone (alpha-MSH) as well as the ultrastructural appearance of IL cells were used as indicators of IL secretory activity. Plasma beta-endorphin levels were also measured to assess the effectiveness of 5-HT-acting drugs. Intraperitoneal administration of 5-hydroxy-L-tryptophan, the synthetic precursor of 5-HT, dramatically elevated the content of 5-HT in the neurointermediate lobe but did not alter plasma titers of alpha-MSH. Treatment with the 5-HT reuptake blocker fluoxetine elevated plasma levels of beta-endorphin but not alpha-MSH. Administration of the 5-HT1/5-HT2 agonist MK-212 produced an elevation in both plasma alpha-MSH and beta-endorphin levels. Quantitative morphometry of IL cells at the ultrastructural level revealed that MK-212 treatment selectively causes depletion of electron-lucent but not electron-dense secretory granules from the cytoplasm of IL cells. Pretreatment with the selective D2 dopamine agonist apomorphine blocked MK-212-induced release of alpha-MSH but not beta-endorphin. Our results show that manipulation of 5-HT synthesis/reuptake does not affect release of alpha-MSH, but that direct activation of 5-HT receptors with the nonselective agonist MK-212 stimulates alpha-MSH release. The ability of apomorphine to block MK-212-induced release of alpha-MSH suggests a direct antagonism between dopaminergic and serotonergic regulation of alpha-MSH release.