ABSTRACT
Although recently developed drugs have brought significant improvement, the treatment of psychotic disorders still presents serious drawbacks. Since inherent complexity and lack of satisfactory understanding of the underlying pathophysiology impose limits for rational drug design, resourceful approaches in the search for antipsychotics are pertinent. This paper reports pharmacological properties of alstonine, a heteroyohimbine type alkaloid, Which exbitited an antipsychotic-like profile, inhibiting amphetamine-induced lethaly, apomorphine-induced steotypy and potentiating barbiturate-induced slleping time. Atypical features of alstonine were the prevention of haloperidol-induced catalepsy and lack of direct interaction with D1, D2 and 5-HT2A receptors, classically linked to antipsychotic mechanism of action.
Subject(s)
Animals , Male , Mice , Antipsychotic Agents/pharmacology , Plants, Medicinal , Secologanin Tryptamine Alkaloids/pharmacology , Amphetamine/antagonists & inhibitors , Apomorphine/antagonists & inhibitors , Barbiturates/antagonists & inhibitors , Central Nervous System Stimulants/antagonists & inhibitors , Chlorpromazine/pharmacology , Clozapine/pharmacology , Diazepam/pharmacology , Emetics/antagonists & inhibitors , Haloperidol/pharmacology , Hypnotics and Sedatives/antagonists & inhibitors , Nigeria , Pentobarbital/pharmacology , Reserpine/pharmacology , Sleep/drug effects , Stereotyping , Sulpiride/pharmacologyABSTRACT
In the present study, the effects of a single administration of buspirone (0.1, 0.3, 1.0, and 3.0 mg/kg sc-30 min before testing) on three dopamine-related behaviors were evaluated in 4-month old male Wistar rats (7-10 animals per group). Buspirone decreased haloperidol (2.0 mg/kg ip)-induced catalepsy in a dose-dependent manner (from 7.30 to 5.09 1n of s compared to the untreated control group). Apomorphine (0.06 mg/kg sc)-induced yawning was also dose-dependently reduced (from 26.7 to 0.9 yawns in 30 min) and so was apomorphine (1.0 mg/kg sc)-induced stereotypy (from 32.9 to 5.9, sum of scores). The present results indicate that buspirone presents unique pharmacological effects related to dopaminergic transmission not only in biochemical but also in behavioral terms
Subject(s)
Animals , Male , Rats , Buspirone/administration & dosage , Catalepsy/drug therapy , Stereotyped Behavior/drug effects , Yawning/drug effects , Analysis of Variance , Apomorphine/antagonists & inhibitors , Buspirone/pharmacology , Catalepsy/chemically induced , Haloperidol/antagonists & inhibitors , Rats, WistarABSTRACT
This study analyzes the changes in the sensitivity of striatal dopaminergic (DA) receptors to apomorphine following withdrawal from long-term treatment with fencamfamine (10 mg/kg, for 40 days). Fencamfamine treatment decreased (34.8 + or - 3.2 vs 25.8 + or - 2.8,P<0.05) the stereotyped behavior induced by apomorfhine (2.0 mg/kg, sc), but potentiated the effect of apomorphine (0.02 mg/kg, sc) in reducing the striatal levels of homovanillic acid (HVA) (0.41 + or - 0.02 micron g/g vs 0.31 + or - 0.03 microng/g, P<0.01) and dihydroxyphenylacetic acid (DOPAC) (0.45 + or - 0.04 microng/g vs 0.34 + or - 0.03 microng/g, P<0.01). These results suggest that changes in pre- or postsynaptic DA receptors may underlie the tolerance and sensitization to the effects of fencamfamine
Subject(s)
Rats , Animals , Male , Apomorphine/antagonists & inhibitors , Central Nervous System Stimulants/pharmacology , Norbornanes/pharmacology , Stereotyped Behavior/drug effects , Corpus Striatum/drug effects , Drug Incompatibility , Drug Tolerance , Norbornanes/administration & dosage , Rats, Inbred Strains , Receptors, DopamineABSTRACT
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.
Subject(s)
Animals , Apomorphine/antagonists & inhibitors , Catalepsy/chemically induced , Fenfluramine/pharmacology , Humans , Male , Methamphetamine/antagonists & inhibitors , Mice , Stereotyped Behavior/drug effectsABSTRACT
The effect of metoclopramide on presynaptic dopamine receptors was investigated in the cat cardioaccelerator nerve preparation. Metoclopramide, a substituted benzamide derivative, antagonized inhibitory action of apomorphine on positive chronotropic responses induced by sympathetic nerve stimulation in cat hearts, in vivo. Neither phentolamine, an alpha-adrenergic blocking agent, nor indomethacin a prostaglandin synthesis inhibitor, antagonized the effect of apomorphine. Apomorphine did not alter the positive chronotropic effects of intravenously administered noradrenaline. Metoclopramide potentiated stimulation-induced positive chronotropic responses. These results suggest that metoclopramide blocks the presynaptic dopamine receptors at the cat heart.