Dopaminergic drugs antagonize the psychotomimetic effects of partial-agonist analgesics

The psychotomimetic actions of the partial-agonist analgesic drugs cyclazocine and levallophan have been demonstrated using a quantitative behavioural test in young rats which measures lateral head movements and pivoting on the hind paws. This drug induced behaviour is antagonized by low doses of the dopaminergic agonists apomorphine and piribedil, the dopamine releasing drug amphetamine, the dopamine reuptake blocking agent benztropine and by large doses of the dopamine precursor L-Dopa. Naloxone antagonize the behaviour, but only at one hundred times the analgesic antagonist dose. These results show that dopaminergic systems are implicated in the mechanism of action of partial-agonist induced psychotomimetic side effects.