Effect of midodrine on chlorpromazine-induced orthostatic hypotension in rabbits: comparison with amezinium, etilefrine and droxidopa.
Orthostatic hypotension was produced in urethane-anesthetized rabbit by a combination of chlorpromazine (0.1 mg/kg, i.v.) and 45 degrees head-up tilt. The effect of midodrine (1 and 3 mg/kg, i.d.) was investigated in comparison with amezinium (10 and 30 mg/kg, i.d.), etilefrine (10 and 30 mg/kg, i.d.) and droxidopa (30 and 100 mg/kg, i.d.). The higher doses of each drug significantly mitigated the chlorpromazine-induced orthostatic hypotension, while none of the lower doses caused a significant effect. The effect of midodrine developed most rapidly; a significant effect was observed 25 min after administration. The order of onset time was midodrine < etilefrine < amezinium < droxidopa. The effect of droxidopa was significant only at 130 to 160 min after administration. The amplitude of effect was in the following order; midodrine = droxidopa > or = etilefrine > amezinium. Midodrine (3 mg/kg, i.d.) mitigated orthostatic hypotension induced by prazosin (0.1 mg/kg, i.v.), but not by pentolinium (0.6 mg/kg, i.v.). It is suggested that midodrine competes with chlorpromazine at alpha1-adrenoceptors and subsequently recovers reflex vasoconstriction. Midodrine may be useful to protect patients with impaired baroreflex activity from accidental orthostatic hypotension during treatment with neuroleptics.
Kurihara
J
J
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa, Japan. jun-kuri@pharm.teikyo-u.ac.jp
Takata
Y
Y
Suzuki
S
S
Okubo
Y
Y
Kato
H
H
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000633:toxicity; D000818:Animals; D000959:Antihypertensive Agents / Q000633:toxicity; D014150:Antipsychotic Agents / Q000633:toxicity*; D001794:Blood Pressure / Q000187:drug effects; D002746:Chlorpromazine / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D015103:Droxidopa / Q000494:pharmacology; D004333:Drug Administration Routes; D004347:Drug Interactions; D004386:Duodenum; D005039:Etilefrine / Q000494:pharmacology; D007024:Hypotension, Orthostatic / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D008879:Midodrine / Q000494:pharmacology*; D010425:Pentolinium Tartrate / Q000633:toxicity; D011224:Prazosin / Q000633:toxicity; D011724:Pyridazines / Q000494:pharmacology; D011817:Rabbits; D013566:Sympathomimetics / Q000494:pharmacology*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000959:Antihypertensive Agents; D014150:Antipsychotic Agents; D011724:Pyridazines; D013566:Sympathomimetics; D008879:Midodrine; D010425:Pentolinium Tartrate; D015103:Droxidopa; C027784:amezinium; D002746:Chlorpromazine; D011224:Prazosin; D005039:Etilefrine